USRE41252E1 - Peptidyl prodrugs and linkers and stabilizers useful therefor - Google Patents
Peptidyl prodrugs and linkers and stabilizers useful therefor Download PDFInfo
- Publication number
- USRE41252E1 USRE41252E1 US12/126,731 US12673108A USRE41252E US RE41252 E1 USRE41252 E1 US RE41252E1 US 12673108 A US12673108 A US 12673108A US RE41252 E USRE41252 E US RE41252E
- Authority
- US
- United States
- Prior art keywords
- substituted
- unsubstituted
- alkyl
- independently selected
- heteroalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime, expires
Links
- 125000001151 peptidyl group Chemical group 0.000 title claims abstract description 14
- 229940002612 prodrug Drugs 0.000 title abstract description 28
- 239000000651 prodrug Substances 0.000 title abstract description 28
- 239000003381 stabilizer Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 226
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 239000003795 chemical substances by application Substances 0.000 claims description 98
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 81
- 238000000034 method Methods 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 72
- 230000008685 targeting Effects 0.000 claims description 61
- 125000001072 heteroaryl group Chemical group 0.000 claims description 50
- 150000007523 nucleic acids Chemical class 0.000 claims description 35
- 108020004707 nucleic acids Proteins 0.000 claims description 32
- 102000039446 nucleic acids Human genes 0.000 claims description 32
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 31
- 125000000524 functional group Chemical group 0.000 claims description 28
- 206010028980 Neoplasm Diseases 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 14
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000001268 conjugating effect Effects 0.000 claims description 5
- 125000002228 disulfide group Chemical group 0.000 claims description 5
- 108090001090 Lectins Proteins 0.000 claims description 4
- 102000004856 Lectins Human genes 0.000 claims description 4
- 239000002523 lectin Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 150000001371 alpha-amino acids Chemical class 0.000 claims description 3
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 230000002147 killing effect Effects 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 102000014187 peptide receptors Human genes 0.000 claims description 2
- 108010011903 peptide receptors Proteins 0.000 claims description 2
- 230000000979 retarding effect Effects 0.000 claims 1
- 239000002619 cytotoxin Substances 0.000 abstract description 64
- 231100000599 cytotoxic agent Toxicity 0.000 abstract description 63
- 229960005501 duocarmycin Drugs 0.000 abstract description 21
- 230000001225 therapeutic effect Effects 0.000 abstract description 21
- 229930184221 duocarmycin Natural products 0.000 abstract description 19
- 238000001727 in vivo Methods 0.000 abstract description 18
- 230000003389 potentiating effect Effects 0.000 abstract description 12
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical class COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 abstract description 9
- 125000005647 linker group Chemical group 0.000 description 109
- -1 poly(ethylene glycol) Polymers 0.000 description 97
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 81
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 72
- 238000005160 1H NMR spectroscopy Methods 0.000 description 65
- 239000003814 drug Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 108090000765 processed proteins & peptides Proteins 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- 235000001014 amino acid Nutrition 0.000 description 45
- 150000001413 amino acids Chemical class 0.000 description 44
- 239000000126 substance Substances 0.000 description 37
- 229940124597 therapeutic agent Drugs 0.000 description 36
- 101710112752 Cytotoxin Proteins 0.000 description 32
- 108090000623 proteins and genes Proteins 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- 230000015572 biosynthetic process Effects 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 27
- 102000004190 Enzymes Human genes 0.000 description 26
- 108090000790 Enzymes Proteins 0.000 description 26
- 230000000694 effects Effects 0.000 description 26
- 229940088598 enzyme Drugs 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000003550 marker Substances 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 23
- 102000004196 processed proteins & peptides Human genes 0.000 description 22
- 238000003776 cleavage reaction Methods 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 20
- 230000007017 scission Effects 0.000 description 20
- 0 [3*]C1CCC2([6*])C([7*])CN(C(=C)/C(C)=C/C3=C(C)C=CC=C3)C2C1.[4*]C.[5*]C Chemical compound [3*]C1CCC2([6*])C([7*])CN(C(=C)/C(C)=C/C3=C(C)C=CC=C3)C2C1.[4*]C.[5*]C 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 241000894007 species Species 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 230000009471 action Effects 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 17
- 150000003254 radicals Chemical class 0.000 description 17
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 16
- 238000007792 addition Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 230000001988 toxicity Effects 0.000 description 16
- 231100000419 toxicity Toxicity 0.000 description 16
- 230000004913 activation Effects 0.000 description 15
- 125000004122 cyclic group Chemical group 0.000 description 15
- 102000035195 Peptidases Human genes 0.000 description 14
- 108091005804 Peptidases Proteins 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 108060005989 Tryptase Proteins 0.000 description 14
- 102000001400 Tryptase Human genes 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- 229920001223 polyethylene glycol Polymers 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 239000004365 Protease Substances 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 230000000692 anti-sense effect Effects 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 125000006850 spacer group Chemical group 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 108091023037 Aptamer Proteins 0.000 description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 description 11
- 230000000087 stabilizing effect Effects 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 10
- 238000006731 degradation reaction Methods 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 235000019419 proteases Nutrition 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229920000858 Cyclodextrin Polymers 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229940127204 compound 29 Drugs 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 235000000346 sugar Nutrition 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 241000282412 Homo Species 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000000032 diagnostic agent Substances 0.000 description 8
- 229940039227 diagnostic agent Drugs 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 7
- 238000001042 affinity chromatography Methods 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000011324 bead Substances 0.000 description 7
- 229940097362 cyclodextrins Drugs 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 6
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 6
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 230000021615 conjugation Effects 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 150000002019 disulfides Chemical class 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 210000002381 plasma Anatomy 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 108060003951 Immunoglobulin Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 125000004474 heteroalkylene group Chemical group 0.000 description 5
- 102000018358 immunoglobulin Human genes 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 108020004491 Antisense DNA Proteins 0.000 description 4
- 108020005544 Antisense RNA Proteins 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 239000003816 antisense DNA Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003184 complementary RNA Substances 0.000 description 4
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 210000003630 histaminocyte Anatomy 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000008177 pharmaceutical agent Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- HYVABZIGRDEKCD-UHFFFAOYSA-N N(6)-dimethylallyladenine Chemical compound CC(C)=CCNC1=NC=NC2=C1N=CN2 HYVABZIGRDEKCD-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001266 acyl halides Chemical class 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 239000000412 dendrimer Substances 0.000 description 3
- 229920000736 dendritic polymer Polymers 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 210000004882 non-tumor cell Anatomy 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 150000004713 phosphodiesters Chemical class 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 231100000057 systemic toxicity Toxicity 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- HPZMWTNATZPBIH-UHFFFAOYSA-N 1-methyladenine Chemical compound CN1C=NC2=NC=NC2=C1N HPZMWTNATZPBIH-UHFFFAOYSA-N 0.000 description 2
- RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 description 2
- YJCJVMMDTBEITC-UHFFFAOYSA-N 10-hydroxycapric acid Chemical compound OCCCCCCCCCC(O)=O YJCJVMMDTBEITC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 description 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 2
- JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 2
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- VLUGXRPLYXZFMF-UHFFFAOYSA-N CC(C)C(=O)C(C)C(C)C(C)SSC(C)(C)C Chemical compound CC(C)C(=O)C(C)C(C)C(C)SSC(C)(C)C VLUGXRPLYXZFMF-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 238000005698 Diels-Alder reaction Methods 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 229940126656 GS-4224 Drugs 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229940040563 agaric acid Drugs 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- ACBQROXDOHKANW-UHFFFAOYSA-N bis(4-nitrophenyl) carbonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)OC1=CC=C([N+]([O-])=O)C=C1 ACBQROXDOHKANW-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 235000013877 carbamide Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001733 carboxylic acid esters Chemical group 0.000 description 2
- 231100000259 cardiotoxicity Toxicity 0.000 description 2
- 230000007681 cardiovascular toxicity Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 2
- 239000005289 controlled pore glass Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 230000009144 enzymatic modification Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 108010073863 saruplase Proteins 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- LAXXPOJCFVMVAX-ZETCQYMHSA-N (2s)-2-amino-4-butylsulfanylbutanoic acid Chemical compound CCCCSCC[C@H](N)C(O)=O LAXXPOJCFVMVAX-ZETCQYMHSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical class C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- SATCOUWSAZBIJO-UHFFFAOYSA-N 1-methyladenine Natural products N=C1N(C)C=NC2=C1NC=N2 SATCOUWSAZBIJO-UHFFFAOYSA-N 0.000 description 1
- WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- KGLPWQKSKUVKMJ-UHFFFAOYSA-N 2,3-dihydrophthalazine-1,4-dione Chemical class C1=CC=C2C(=O)NNC(=O)C2=C1 KGLPWQKSKUVKMJ-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- HLYBTPMYFWWNJN-UHFFFAOYSA-N 2-(2,4-dioxo-1h-pyrimidin-5-yl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CNC(=O)NC1=O HLYBTPMYFWWNJN-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- SGAKLDIYNFXTCK-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=O)NC1=O SGAKLDIYNFXTCK-UHFFFAOYSA-N 0.000 description 1
- SVBOROZXXYRWJL-UHFFFAOYSA-N 2-[(4-oxo-2-sulfanylidene-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=S)NC1=O SVBOROZXXYRWJL-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ZJGBFJBMTKEFNQ-UHFFFAOYSA-N 3-(2,5-dioxopyrrol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 ZJGBFJBMTKEFNQ-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 1
- GJAKJCICANKRFD-UHFFFAOYSA-N 4-acetyl-4-amino-1,3-dihydropyrimidin-2-one Chemical compound CC(=O)C1(N)NC(=O)NC=C1 GJAKJCICANKRFD-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- MQJSSLBGAQJNER-UHFFFAOYSA-N 5-(methylaminomethyl)-1h-pyrimidine-2,4-dione Chemical compound CNCC1=CNC(=O)NC1=O MQJSSLBGAQJNER-UHFFFAOYSA-N 0.000 description 1
- WPYRHVXCOQLYLY-UHFFFAOYSA-N 5-[(methoxyamino)methyl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CONCC1=CNC(=S)NC1=O WPYRHVXCOQLYLY-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- SUTWPJHCRAITLU-UHFFFAOYSA-N 6-aminohexan-1-ol Chemical compound NCCCCCCO SUTWPJHCRAITLU-UHFFFAOYSA-N 0.000 description 1
- CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 description 1
- UGZAJZLUKVKCBM-UHFFFAOYSA-N 6-sulfanylhexan-1-ol Chemical compound OCCCCCCS UGZAJZLUKVKCBM-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 241000607620 Aliivibrio fischeri Species 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108090000531 Amidohydrolases Proteins 0.000 description 1
- 102000004092 Amidohydrolases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- RVUSHSPZJUACSR-QOASWNAHSA-N B.C.C.C.CCCCN(CCSSC(C)(C)CC(=O)NCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O)C(=O)OC1=CC2=C(C3=C1N/C(C)=C\3C(=O)OC)[C@H](CCl)CN2C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.CCCCNCCSSC(C)(C)CC(=O)NCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O.COC(=O)/C1=C(\C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)O2)C[C@H]1CCl.COC(=O)/C1=C(\C)NC2=C1[C@@]13C[C@@H]1CN(C(=O)C1=CC4=C(C=CC([N+](=O)[O-])=C4)O1)C3=CC2=O.COC(=O)/C1=C(\C)NC2=C1[C@@]13C[C@@H]1CNC3=CC2=O.Cl.O=C(O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.O=C(OC1=CC=C([N+](=O)[O-])C=C1)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.O=[N+]([O-])C1=CC=C(O)C=C1 Chemical compound B.C.C.C.CCCCN(CCSSC(C)(C)CC(=O)NCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O)C(=O)OC1=CC2=C(C3=C1N/C(C)=C\3C(=O)OC)[C@H](CCl)CN2C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.CCCCNCCSSC(C)(C)CC(=O)NCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O.COC(=O)/C1=C(\C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)O2)C[C@H]1CCl.COC(=O)/C1=C(\C)NC2=C1[C@@]13C[C@@H]1CN(C(=O)C1=CC4=C(C=CC([N+](=O)[O-])=C4)O1)C3=CC2=O.COC(=O)/C1=C(\C)NC2=C1[C@@]13C[C@@H]1CNC3=CC2=O.Cl.O=C(O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.O=C(OC1=CC=C([N+](=O)[O-])C=C1)C1=CC2=C(C=CC([N+](=O)[O-])=C2)O1.O=[N+]([O-])C1=CC=C(O)C=C1 RVUSHSPZJUACSR-QOASWNAHSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- OSVFNTRHIHMYRO-UHFFFAOYSA-N C.C.CC(C)C1=C(C(C)C)C23CC2CN(C(C)C)C3=CC1=O.CCC1CN(C(C)C)C2=C1C(C(C)C)=C(C(C)C)C(O)=C2 Chemical compound C.C.CC(C)C1=C(C(C)C)C23CC2CN(C(C)C)C3=CC1=O.CCC1CN(C(C)C)C2=C1C(C(C)C)=C(C(C)C)C(O)=C2 OSVFNTRHIHMYRO-UHFFFAOYSA-N 0.000 description 1
- WYGCEHREKDXJNL-UHFFFAOYSA-N C.C.CCCCCCC(C)=O Chemical compound C.C.CCCCCCC(C)=O WYGCEHREKDXJNL-UHFFFAOYSA-N 0.000 description 1
- ZWAUWGGFVRLNCZ-JMHRFLNMSA-N C.CCN(CCNN[C@@H](C=O)CC(C)C)C(=O)OC1=C(OC)C=CC(CCC2=CC(OC)=C(OC)C(OC)=C2)=C1.CCNCCN.CCNCCNC(=O)[C@@H](CC(C)C)NC(=O)OC(C)(C)C.COC1=CC(CCC2=CC(OC(=O)OC3=CC=C([N+](=O)[O-])C=C3)=C(OC)C=C2)=CC(OC)=C1OC Chemical compound C.CCN(CCNN[C@@H](C=O)CC(C)C)C(=O)OC1=C(OC)C=CC(CCC2=CC(OC)=C(OC)C(OC)=C2)=C1.CCNCCN.CCNCCNC(=O)[C@@H](CC(C)C)NC(=O)OC(C)(C)C.COC1=CC(CCC2=CC(OC(=O)OC3=CC=C([N+](=O)[O-])C=C3)=C(OC)C=C2)=CC(OC)=C1OC ZWAUWGGFVRLNCZ-JMHRFLNMSA-N 0.000 description 1
- IYLLTGVXOVKVBN-ZIHWAWJOSA-M C1=CN=C(SSC2=NC=CC=C2)C=C1.CCCCN(CCS)C(=O)OC(C)(C)C.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=C(OC)C=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=C1.CCCCN(CCSSC(C)(C)CC(=O)O)C(=O)OC(C)(C)C.CCCCN(CCSSC(C)(C)CC(=O)OC)C(=O)OC(C)(C)C.CCCCN(CCSSC1=NC=CC=C1)C(=O)OC(C)(C)C.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.COC(=O)CC(C)(C)S.COC1=CC=C(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)C=C1OC(=O)OC1=CC=C([N+](=O)[O-])C=C1.NCN1C(=O)C=CC1=O.[Li]O Chemical compound C1=CN=C(SSC2=NC=CC=C2)C=C1.CCCCN(CCS)C(=O)OC(C)(C)C.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=C(OC)C=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=C1.CCCCN(CCSSC(C)(C)CC(=O)O)C(=O)OC(C)(C)C.CCCCN(CCSSC(C)(C)CC(=O)OC)C(=O)OC(C)(C)C.CCCCN(CCSSC1=NC=CC=C1)C(=O)OC(C)(C)C.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.COC(=O)CC(C)(C)S.COC1=CC=C(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)C=C1OC(=O)OC1=CC=C([N+](=O)[O-])C=C1.NCN1C(=O)C=CC1=O.[Li]O IYLLTGVXOVKVBN-ZIHWAWJOSA-M 0.000 description 1
- GIQUMTPHMRKZIJ-BOPOOPDGSA-N CC(C)(C)[Si](C)(C)OC1=CC=C(CBr)C=C1.CCC1=CC=C(OC(=O)N(CC)CCNC(=O)[C@@H](CC(C)C)NC(=O)OC(C)(C)C)C=C1.CCC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1.CO Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(CBr)C=C1.CCC1=CC=C(OC(=O)N(CC)CCNC(=O)[C@@H](CC(C)C)NC(=O)OC(C)(C)C)C=C1.CCC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1.CO GIQUMTPHMRKZIJ-BOPOOPDGSA-N 0.000 description 1
- CHTWJCWWXXVVAW-UHFFFAOYSA-N CC(C)(C)[Si](C)(C)OC1=CC=C(CBr)C=C1.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=CC=C(COC)C=C1.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)CC(SC)C1=O)C(=O)OC1=CC=C(COC)C=C1.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.CO.COCC1=CC=C(O)C=C1.COCC1=CC=C(OC(=O)OC2=CC=C([N+](=O)[O-])C=C2)C=C1.COCC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(CBr)C=C1.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=CC=C(COC)C=C1.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)CC(SC)C1=O)C(=O)OC1=CC=C(COC)C=C1.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.CO.COCC1=CC=C(O)C=C1.COCC1=CC=C(OC(=O)OC2=CC=C([N+](=O)[O-])C=C2)C=C1.COCC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 CHTWJCWWXXVVAW-UHFFFAOYSA-N 0.000 description 1
- HKQRRJKKBZBHDA-UHFFFAOYSA-N CC(SSC(C)(C)C)C(C)N(C)C(=O)OC(C)(C)C Chemical compound CC(SSC(C)(C)C)C(C)N(C)C(=O)OC(C)(C)C HKQRRJKKBZBHDA-UHFFFAOYSA-N 0.000 description 1
- WIPXRPKZOBLEPF-UHFFFAOYSA-N CC.CC(SSC(C)(C)C)C(C)N(C)C(=O)OC1=CC=C(COC(C)(C)C)C=C1 Chemical compound CC.CC(SSC(C)(C)C)C(C)N(C)C(=O)OC1=CC=C(COC(C)(C)C)C=C1 WIPXRPKZOBLEPF-UHFFFAOYSA-N 0.000 description 1
- CATSNJVOTSVZJV-UHFFFAOYSA-N CCCCCC(C)=O Chemical compound CCCCCC(C)=O CATSNJVOTSVZJV-UHFFFAOYSA-N 0.000 description 1
- ZPVFWPFBNIEHGJ-UHFFFAOYSA-N CCCCCCC(C)=O Chemical compound CCCCCCC(C)=O ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 0.000 description 1
- RYQUXNWPDPZOSM-WFJREZPYSA-N CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=C2NC(C)=C(C(=O)OC)C2=C2C(=C1)N(C(=O)C1=CC3=C(C=CC([N+](=O)[O-])=C3)N1)C[C@H]2CCl.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)CC(SC)C1=O)C(=O)OC1=C2NC(C)=C(C(=O)OC)C2=C2C(=C1)N(C(=O)C1=CC3=C(C=CC([N+](=O)[O-])=C3)N1)C[C@H]2CCl.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.COC(=O)C1=C(C)NC2=C(O)C=C3C(=C21)[C@H](CCl)CN3C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.COC(=O)C1=C(C)NC2=C(OC(=O)OC3=CC=C([N+](=O)[O-])C=C3)C=C3C(=C21)[C@H](CCl)CN3C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 Chemical compound CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O)C(=O)OC1=C2NC(C)=C(C(=O)OC)C2=C2C(=C1)N(C(=O)C1=CC3=C(C=CC([N+](=O)[O-])=C3)N1)C[C@H]2CCl.CCCCN(CCSSC(C)(C)CC(=O)NCN1C(=O)CC(SC)C1=O)C(=O)OC1=C2NC(C)=C(C(=O)OC)C2=C2C(=C1)N(C(=O)C1=CC3=C(C=CC([N+](=O)[O-])=C3)N1)C[C@H]2CCl.CCCCNCCSSC(C)(C)CC(=O)NCN1C(=O)C=CC1=O.CCN(CC)CC.COC(=O)C1=C(C)NC2=C(O)C=C3C(=C21)[C@H](CCl)CN3C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.COC(=O)C1=C(C)NC2=C(OC(=O)OC3=CC=C([N+](=O)[O-])C=C3)C=C3C(=C21)[C@H](CCl)CN3C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 RYQUXNWPDPZOSM-WFJREZPYSA-N 0.000 description 1
- HSWFSRAJUDCFQD-FTNGTIOUSA-N CCN(CC)CC.CCN(CCNC)C(=O)OC1=CC2=C(C3=C1NC(C)=C3C(=O)OC)[C@H](CCl)CN2C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.CCNCCNC.CNCCC(=O)OC1=CC2=C(C3=C1NC(C)=C3C(=O)OC)C(CCl)CN2C(C)C.COC(=O)C1=C(C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)N2)C[C@H]1CCl.COC(=O)C1=C(C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)O2)CC1CCl.COC(=O)C1=C(C)NC2=C1C1=C(C=C2OC(=O)OC2=CC=C([N+](=O)[O-])C=C2)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)N2)C[C@H]1CCl.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 Chemical compound CCN(CC)CC.CCN(CCNC)C(=O)OC1=CC2=C(C3=C1NC(C)=C3C(=O)OC)[C@H](CCl)CN2C(=O)C1=CC2=C(C=CC([N+](=O)[O-])=C2)N1.CCNCCNC.CNCCC(=O)OC1=CC2=C(C3=C1NC(C)=C3C(=O)OC)C(CCl)CN2C(C)C.COC(=O)C1=C(C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)N2)C[C@H]1CCl.COC(=O)C1=C(C)NC2=C1C1=C(C=C2O)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)O2)CC1CCl.COC(=O)C1=C(C)NC2=C1C1=C(C=C2OC(=O)OC2=CC=C([N+](=O)[O-])C=C2)N(C(=O)C2=CC3=C(C=CC([N+](=O)[O-])=C3)N2)C[C@H]1CCl.O=C(Cl)OC1=CC=C([N+](=O)[O-])C=C1 HSWFSRAJUDCFQD-FTNGTIOUSA-N 0.000 description 1
- HSRUWLHNZHFDJX-UHFFFAOYSA-N CCSSCCC(C)=O Chemical compound CCSSCCC(C)=O HSRUWLHNZHFDJX-UHFFFAOYSA-N 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000192700 Cyanobacteria Species 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000007118 DNA alkylation Effects 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 241000941423 Grom virus Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical group ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical group OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical group C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Chemical group CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 231100000678 Mycotoxin Toxicity 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
- 150000001199 N-acyl amides Chemical class 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- BVMWIXWOIGJRGE-UHFFFAOYSA-N NP(O)=O Chemical class NP(O)=O BVMWIXWOIGJRGE-UHFFFAOYSA-N 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical class OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- WSDRAZIPGVLSNP-UHFFFAOYSA-N O.P(=O)(O)(O)O.O.O.P(=O)(O)(O)O Chemical compound O.P(=O)(O)(O)O.O.O.P(=O)(O)(O)O WSDRAZIPGVLSNP-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 241001315609 Pittosporum crassifolium Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 102100037136 Proteinase-activated receptor 1 Human genes 0.000 description 1
- 101710121440 Proteinase-activated receptor 1 Proteins 0.000 description 1
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 1
- 101710121435 Proteinase-activated receptor 2 Proteins 0.000 description 1
- 108091007187 Reductases Proteins 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000133426 Streptomyces zelensis Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000200270 Symbiodinium sp. Species 0.000 description 1
- 241000192707 Synechococcus Species 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 description 1
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- HKNSIVFWRXBWCK-UHFFFAOYSA-N [N].NC1=CC=CC=C1 Chemical compound [N].NC1=CC=CC=C1 HKNSIVFWRXBWCK-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 150000001361 allenes Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- IVHKZGYFKJRXBD-UHFFFAOYSA-N amino carbamate Chemical compound NOC(N)=O IVHKZGYFKJRXBD-UHFFFAOYSA-N 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229960002519 amoxapine Drugs 0.000 description 1
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 125000005337 azoxy group Chemical group [N+]([O-])(=N*)* 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- KVUAALJSMIVURS-ZEDZUCNESA-N calcium;(2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-N 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- MSPRUJDUTKRMLM-UHFFFAOYSA-N caroverine Chemical compound O=C1N(CCN(CC)CC)C2=CC=CC=C2N=C1CC1=CC=C(OC)C=C1 MSPRUJDUTKRMLM-UHFFFAOYSA-N 0.000 description 1
- 229960003355 caroverine Drugs 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 208000023819 chronic asthma Diseases 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000004814 combretastatins Chemical class 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000001913 cyanates Chemical class 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical class OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 108010083141 dipeptidyl carboxypeptidase Proteins 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960005426 doxepin Drugs 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229930182817 methionine Chemical group 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- IZAGSTRIDUNNOY-UHFFFAOYSA-N methyl 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetate Chemical compound COC(=O)COC1=CNC(=O)NC1=O IZAGSTRIDUNNOY-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000002636 mycotoxin Substances 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 125000005506 phthalide group Chemical class 0.000 description 1
- 108060006184 phycobiliprotein Proteins 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000004375 physisorption Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229960002601 protriptyline Drugs 0.000 description 1
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 239000000718 radiation-protective agent Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000019705 regulation of vascular permeability Effects 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003459 sulfonic acid esters Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000005555 sulfoximide group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
- 229960003991 trazodone Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 229960002431 trimipramine Drugs 0.000 description 1
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 1
- SYHDSBBKRLVLFF-UHFFFAOYSA-N triparanol Chemical class C1=CC(OCCN(CC)CC)=CC=C1C(O)(C=1C=CC(C)=CC=1)CC1=CC=C(Cl)C=C1 SYHDSBBKRLVLFF-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- WCNMEQDMUYVWMJ-JPZHCBQBSA-N wybutoxosine Chemical compound C1=NC=2C(=O)N3C(CC([C@H](NC(=O)OC)C(=O)OC)OO)=C(C)N=C3N(C)C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WCNMEQDMUYVWMJ-JPZHCBQBSA-N 0.000 description 1
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Abstract
Description
in which ring system A is a member selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl groups. The symbols E and G represent H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, a heteroatom, or a single bond. E and G are optionally joined to form a ring system selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl.
in which ring system A is a member selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl groups. Exemplary ring systems include phenyl and pyrrole.
wherein R30 is a member selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl. The symbols R31 and R32 independently represent H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, or R31 and R32 together are:
R33 and R34 independently represent H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. The symbol R35 represents substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl or NR36. R36 is a member selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl. X5 is O or NR37, wherein R37 is a member selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl. In yet a further embodiment, at least one of R33 and R34 is selected from L5X6, wherein the identity of “L” and “X” is generally as described herein.
In the formula above, the symbols X2 and Z1 represent members independently selected from O, S and NR23. The groups R17 and R18 are independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, halogen, NO2, NR19R20, NC(O)R19, OC(O)NR19, OC(O)OR19, C(O)R19, SR19 or OR19.
In this embodiment, the identities of the radicals R3, R4, R5, R6, R7 and X are substantially as described above. The symbol Z is a member independently selected from O, S and NR23. The symbol R23 represents a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and acyl. When both X and Z are NR23, each R23 is independently selected. The symbol R1 represents H, substituted or unsubstituted lower alkyl, or C(O)R8, R8 is a member selected from NR9R10, NR9NHR10 and OR9. R9, and R10 are independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl. The radical R2 is H, or substituted or unsubstituted lower alkyl. It is generally preferred that when R2 is substituted alkyl, it is other than perfluoroalkyl, e.g., CF3.
In the Formulae above, X is preferably O; and Z is preferably O.
(L1)q AA1--Ab AAb+1—(L2)v—X3. (VII)
in which, the symbols R21 and R22 independently represent substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, detectable labels and targeting agents. The groups R12, and R25 are independently selected from H, substituted or unsubstituted lower alkyl, an amino acid side chain, detectable labels, and targeting agents. The amino acid portion of the structure, represented by AA1, AAb and AAb+1 is substantially similar to that of Formula VII.
in which X4 is a member selected from protected reactive functional groups, unprotected reactive functional groups, detectable labels and targeting agents. L3 is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl groups, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl. L4 is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl groups, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl. The symbols p and t represent integers independently selected from 0 and 1.
as illustrated by
wherein R27 and R28 are members independently selected from H, substituted or unsubstituted lower alkyl, amino acid side chains, detectable labels and targeting agents; and s is an integer in the range of 0 to 6.
in which X4 is a member selected from protected reactive functional groups, unprotected reactive functional groups, detectable labels and targeting agents. L3 is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl groups. L4 is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl groups. The symbols p and t represent integers independently selected from 0 and 1.
wherein R30 represents substituted or unsubstituted alkyl terminated with a reactive functional group, substituted or unsubstituted heteroaryl terminated with a functional group and -(L3)pX4, wherein each L3, X4 and p are independently selected.
In the formula above, the symbol E represents an enzymatically cleaveable moiety (e.g., peptide, disulfide, ester, etc.). The symbols R, RI, RII and RIII represent members that include, for example, H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, poly(ethyleneglycol), acyl, a targeting agent, or a detectable label. In an exemplary embodiment, the carbonyl moiety is tethered to a moiety that is a detectable label, a therapeutic moiety or a solid support. The carbonyl moiety may be further attached to an oxygen, sulfur, nitrogen or carbon at the position where the fragment is truncated. In a further exemplary embodiment, the carbonyl moiety is a component of a urethane. The oxygen tethered to the carbonyl moiety is attached to a targeting agent, cytotoxins, solid support or the like.
Peptide-Based Linkers
1.2 Synthetic Methodology
Claims (32)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/126,731 USRE41252E1 (en) | 2001-05-31 | 2008-05-23 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29525901P | 2001-05-31 | 2001-05-31 | |
US29534201P | 2001-05-31 | 2001-05-31 | |
US29519601P | 2001-05-31 | 2001-05-31 | |
US30490801P | 2001-07-11 | 2001-07-11 | |
US10/161,234 US7087600B2 (en) | 2001-05-31 | 2002-05-31 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
US12/126,731 USRE41252E1 (en) | 2001-05-31 | 2008-05-23 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/161,234 Reissue US7087600B2 (en) | 2001-05-31 | 2002-05-31 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Publications (1)
Publication Number | Publication Date |
---|---|
USRE41252E1 true USRE41252E1 (en) | 2010-04-20 |
Family
ID=27501653
Family Applications (8)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/160,972 Expired - Lifetime US7129261B2 (en) | 2001-05-31 | 2002-05-31 | Cytotoxic agents |
US10/161,234 Ceased US7087600B2 (en) | 2001-05-31 | 2002-05-31 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
US10/161,233 Expired - Lifetime US6989452B2 (en) | 2001-05-31 | 2002-05-31 | Disulfide prodrugs and linkers and stabilizers useful therefor |
US11/133,970 Expired - Lifetime US7498302B2 (en) | 2001-05-31 | 2005-06-21 | Disulfide prodrugs and linkers and stabilizers useful therefor |
US11/224,580 Expired - Lifetime US7507420B2 (en) | 2001-05-31 | 2005-09-12 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
US12/126,731 Expired - Lifetime USRE41252E1 (en) | 2001-05-31 | 2008-05-23 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
US12/396,266 Expired - Fee Related US8034959B2 (en) | 2001-05-31 | 2009-03-02 | Methods of treating cancer with an antibody-drug conjugate |
US12/397,834 Expired - Fee Related US7977465B2 (en) | 2001-05-31 | 2009-03-04 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Family Applications Before (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/160,972 Expired - Lifetime US7129261B2 (en) | 2001-05-31 | 2002-05-31 | Cytotoxic agents |
US10/161,234 Ceased US7087600B2 (en) | 2001-05-31 | 2002-05-31 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
US10/161,233 Expired - Lifetime US6989452B2 (en) | 2001-05-31 | 2002-05-31 | Disulfide prodrugs and linkers and stabilizers useful therefor |
US11/133,970 Expired - Lifetime US7498302B2 (en) | 2001-05-31 | 2005-06-21 | Disulfide prodrugs and linkers and stabilizers useful therefor |
US11/224,580 Expired - Lifetime US7507420B2 (en) | 2001-05-31 | 2005-09-12 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/396,266 Expired - Fee Related US8034959B2 (en) | 2001-05-31 | 2009-03-02 | Methods of treating cancer with an antibody-drug conjugate |
US12/397,834 Expired - Fee Related US7977465B2 (en) | 2001-05-31 | 2009-03-04 | Peptidyl prodrugs and linkers and stabilizers useful therefor |
Country Status (11)
Country | Link |
---|---|
US (8) | US7129261B2 (en) |
EP (2) | EP1434778A4 (en) |
JP (2) | JP4961095B2 (en) |
KR (1) | KR20030033007A (en) |
CN (2) | CN101671335A (en) |
AU (1) | AU2002303929B9 (en) |
CA (1) | CA2448319C (en) |
IL (2) | IL154183A0 (en) |
MX (1) | MXPA03011094A (en) |
NZ (1) | NZ529788A (en) |
WO (1) | WO2002096910A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012162482A1 (en) | 2011-05-26 | 2012-11-29 | Bristol-Myers Squibb Company | Immunoconjugates, compositions containing them, and methods of making and use |
Families Citing this family (224)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7425541B2 (en) * | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
EP1408960B1 (en) * | 2001-02-22 | 2006-05-31 | School Of Pharmacy, University Of London | Benz-indole and benzo-quinoline derivatives as prodrugs for tumour treatment |
ES2552281T3 (en) | 2001-05-11 | 2015-11-26 | Ludwig Institute For Cancer Research Ltd. | Specific binding proteins and uses thereof |
US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
US7129261B2 (en) * | 2001-05-31 | 2006-10-31 | Medarex, Inc. | Cytotoxic agents |
US20100311954A1 (en) * | 2002-03-01 | 2010-12-09 | Xencor, Inc. | Optimized Proteins that Target Ep-CAM |
KR20050009751A (en) * | 2002-06-14 | 2005-01-25 | 다케다 야쿠힌 고교 가부시키가이샤 | Prodrugs of imidazole derivatives, for use as proton pump inhibitors in the treatment of e.g. peptic ulcers |
US20040249130A1 (en) * | 2002-06-18 | 2004-12-09 | Martin Stanton | Aptamer-toxin molecules and methods for using same |
EP1386927B1 (en) * | 2002-08-02 | 2005-03-30 | Institut Curie | Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to GB3 expressing tumors |
US8853376B2 (en) | 2002-11-21 | 2014-10-07 | Archemix Llc | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
WO2004073843A1 (en) * | 2003-02-19 | 2004-09-02 | Mcmaster University | Composite materials comprising supported porous gels |
ZA200507752B (en) * | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
WO2004093807A2 (en) | 2003-04-22 | 2004-11-04 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Somatostatin vectors |
CA2536357A1 (en) | 2003-05-29 | 2004-12-23 | The Scripps Research Institute | Targeted delivery to legumain-expressing cells |
JP5189765B2 (en) * | 2003-08-01 | 2013-04-24 | バイオコン・リミテッド | Aryl carbamate oligomers for hydrolyzable prodrugs and prodrugs containing the same |
US8101720B2 (en) | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
US8883147B2 (en) | 2004-10-21 | 2014-11-11 | Xencor, Inc. | Immunoglobulins insertions, deletions, and substitutions |
US20060134105A1 (en) * | 2004-10-21 | 2006-06-22 | Xencor, Inc. | IgG immunoglobulin variants with optimized effector function |
US8399618B2 (en) | 2004-10-21 | 2013-03-19 | Xencor, Inc. | Immunoglobulin insertions, deletions, and substitutions |
EP1758671B9 (en) | 2004-04-08 | 2014-02-19 | Natrix Separations Inc. | Membrane stacks |
US20050239864A1 (en) * | 2004-04-23 | 2005-10-27 | Yuqiang Wang | Novel tumor-selective chemotherapeutic agents |
EP1747021B1 (en) * | 2004-05-19 | 2015-09-09 | E. R. Squibb & Sons, L.L.C. | Self-immolative linkers and drug conjugates |
US7691962B2 (en) * | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
WO2005120701A1 (en) * | 2004-06-07 | 2005-12-22 | Mcmaster University | Stable composite material comprising supported porous gels |
BRPI0512928A (en) * | 2004-06-30 | 2008-04-15 | Novartis Ag | compositions and methods for releasing antitumor agents |
CN102746404B (en) | 2004-11-12 | 2016-01-20 | 赞科股份有限公司 | To FcRn in conjunction with reformed Fc variant |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
AU2006214031A1 (en) * | 2005-02-18 | 2006-08-24 | Medarex, Inc. | Human monoclonal antibodies to prostate specific membrane antigen (PSMA) |
US7714016B2 (en) * | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
EP2308839B1 (en) | 2005-04-20 | 2017-03-01 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compounds |
ES2579235T3 (en) | 2005-06-29 | 2016-08-08 | Threshold Pharmaceuticals, Inc. | Phosphoramidate Alkylating Prodrugs |
WO2007008943A2 (en) | 2005-07-08 | 2007-01-18 | Xencor, Inc. | Optimized anti-ep-cam antibodies |
EP1934261B1 (en) * | 2005-09-26 | 2014-10-29 | Medarex, L.L.C. | Human monoclonal antibodies to cd70 |
CN101312748A (en) * | 2005-09-26 | 2008-11-26 | 梅达莱克斯公司 | Antibody-drug conjugates and methods of use |
ES2375843T3 (en) | 2005-10-26 | 2012-03-06 | Medarex, Inc. | PROCEDURES AND COMPOUNDS FOR THE PREPARATION OF ANC? LOGOS OF CC-1065. |
WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
DK1957539T3 (en) | 2005-12-08 | 2013-05-06 | Medarex Inc | HUMAN MONOCLONAL ANTIBODIES FOR PROTEINTYROSINKINASE 7 (PTK7) AND THEIR USE |
PT1960434E (en) | 2005-12-08 | 2012-10-02 | Medarex Inc | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 |
US20090175886A1 (en) | 2006-01-17 | 2009-07-09 | Medarex, Inc. | Monoclonal antibodies against cd30 lacking in fucosyl and xylosyl residues |
US9603941B2 (en) * | 2006-01-24 | 2017-03-28 | Minghui Chai | Method of preparing dendritic drugs |
RU2489423C2 (en) * | 2006-02-02 | 2013-08-10 | Синтарга Б.В. | Water-soluble analogues cc-1065 and their conjugates |
DK2383297T5 (en) | 2006-08-14 | 2022-07-04 | Xencor Inc | Optimized antibodies directed against CD19 |
US20110182904A1 (en) | 2006-09-05 | 2011-07-28 | Deborah Zimmerman | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
MX2009005776A (en) | 2006-12-01 | 2009-06-10 | Medarex Inc | Human antibodies that bind cd22 and uses thereof. |
CL2007003622A1 (en) | 2006-12-13 | 2009-08-07 | Medarex Inc | Human anti-cd19 monoclonal antibody; composition comprising it; and tumor cell growth inhibition method. |
WO2008074004A2 (en) * | 2006-12-14 | 2008-06-19 | Medarex, Inc. | Human antibodies that bind cd70 and uses thereof |
ES2884044T3 (en) * | 2006-12-26 | 2021-12-10 | Immunogenesis Inc | Phosphoramidate alkylating prodrug for cancer treatment |
TWI412367B (en) * | 2006-12-28 | 2013-10-21 | Medarex Llc | Chemical linkers and cleavable substrates and conjugates thereof |
US9090693B2 (en) * | 2007-01-25 | 2015-07-28 | Dana-Farber Cancer Institute | Use of anti-EGFR antibodies in treatment of EGFR mutant mediated disease |
WO2008103693A2 (en) * | 2007-02-21 | 2008-08-28 | Medarex, Inc. | Chemical linkers with single amino acids and conjugates thereof |
MX2009009782A (en) * | 2007-03-15 | 2010-09-10 | Ludwig Inst Cancer Res | Treatment method using egfr antibodies and src inhibitors and related formulations. |
LT2176298T (en) | 2007-05-30 | 2018-04-10 | Xencor, Inc. | Methods and compositions for inhibiting cd32b expressing cells |
US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
WO2009023265A1 (en) | 2007-08-14 | 2009-02-19 | Ludwig Institute For Cancer Research | Monoclonal antibody 175 targeting the egf receptor and derivatives and uses thereof |
EP2185188B1 (en) | 2007-08-22 | 2014-08-06 | Medarex, L.L.C. | Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions |
CN101951946B (en) | 2007-10-01 | 2014-12-10 | 百时美施贵宝公司 | Human antibodies that bind mesothelin, and uses thereof |
US20090118031A1 (en) * | 2007-11-01 | 2009-05-07 | Qualizza Gregory K | Shaft Structure with Configurable Bending Profile |
CL2008003525A1 (en) * | 2007-11-30 | 2010-01-22 | Medarex Inc | Human anti-rg1 monoclonal antibody conjugate or an antigen-binding portion thereof with associated molecules, which composition comprises; in vitro method for inhibiting the growth of a tumor cell expressing rg-1; use of this conjugate to treat cancer |
US20110152252A1 (en) * | 2007-12-18 | 2011-06-23 | Institut Curie | Shiga toxin b-subunit/chemotherapeutics conjugates |
SI2808343T1 (en) | 2007-12-26 | 2019-10-30 | Xencor Inc | Fc variants with altered binding to FcRn |
US8246538B2 (en) * | 2008-02-28 | 2012-08-21 | K2M, Inc. | Minimally invasive retractor with separable blades and methods of use |
WO2009143299A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Hepatoprotectant acetaminophen mutual prodrugs |
AR072999A1 (en) | 2008-08-11 | 2010-10-06 | Medarex Inc | HUMAN ANTIBODIES THAT JOIN GEN 3 OF LYMPHOCYTARY ACTIVATION (LAG-3) AND THE USES OF THESE |
AU2009288234B2 (en) | 2008-09-02 | 2014-08-21 | Merck Millipore Ltd. | Chromatography membranes, devices containing them, and methods of use thereof |
HUE035798T2 (en) * | 2008-11-03 | 2018-05-28 | Syntarga Bv | Cc-1065 analogs and their conjugates |
US9238878B2 (en) | 2009-02-17 | 2016-01-19 | Redwood Bioscience, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
BRPI1009232B1 (en) | 2009-03-05 | 2022-05-03 | E.R. Squibb & Sons, Llc. | Isolated monoclonal antibody or an antigen-binding portion thereof, or an antibody fragment, composition comprising them, nucleic acid molecule, hybridoma and methods for preparing an anti-cadm1 antibody |
EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
SG10201401604VA (en) | 2009-04-20 | 2014-08-28 | Oxford Biotherapeutics Ltd | Antibodies Specific To Cadherin-17 |
US8394922B2 (en) | 2009-08-03 | 2013-03-12 | Medarex, Inc. | Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof |
US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
US20110076232A1 (en) * | 2009-09-29 | 2011-03-31 | Ludwig Institute For Cancer Research | Specific binding proteins and uses thereof |
EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
WO2011054007A1 (en) | 2009-11-02 | 2011-05-05 | Oxford Biotherapeutics Ltd. | Ror1 as therapeutic and diagnostic target |
WO2011058439A1 (en) * | 2009-11-13 | 2011-05-19 | Natrix Separations, Inc. | Hydrophobic interaction chromatography membranes, and methods of use thereof |
US9023996B2 (en) | 2009-12-23 | 2015-05-05 | Synimmune Gmbh | Anti-FLT3 antibodies |
WO2011089211A1 (en) | 2010-01-22 | 2011-07-28 | Synimmune Gmbh | Anti-cd133 antibodies and methods of using the same |
WO2011103421A1 (en) * | 2010-02-18 | 2011-08-25 | Shuber Anthony P | Compositions and methods for treating cancer |
UA112291C2 (en) | 2010-04-21 | 2016-08-25 | Синтарґа Б.В. | Novel conjugates of cc-1065 analogs and bifunctional linkers |
CA2800769C (en) | 2010-05-27 | 2021-11-02 | Genmab A/S | Monoclonal antibodies against her2 epitope |
AU2011257121A1 (en) | 2010-05-27 | 2013-01-10 | Genmab A/S | Monoclonal antibodies against HER2 |
JP6055404B2 (en) | 2010-06-15 | 2016-12-27 | ゲンマブ エー/エス | Human antibody drug conjugates against tissue factor |
JP5953303B2 (en) | 2010-07-29 | 2016-07-20 | ゼンコア インコーポレイテッド | Antibodies with modified isoelectric points |
US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
US9228023B2 (en) | 2010-10-01 | 2016-01-05 | Oxford Biotherapeutics Ltd. | Anti-ROR1 antibodies and methods of use for treatment of cancer |
JOP20210044A1 (en) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | Anti-cd38 antibodies |
RU2606016C2 (en) | 2011-01-14 | 2017-01-10 | Редвуд Байосайнс, Инк. | Aldehyde marked immunoglobulin polypeptides and methods of their application |
US8987412B2 (en) * | 2011-03-04 | 2015-03-24 | New York University | Hydrogen bond surrogate macrocycles as modulators of Ras |
CN103796678B (en) | 2011-04-20 | 2018-02-27 | 健玛保 | For HER2 bispecific antibody |
JP6272755B2 (en) | 2011-05-17 | 2018-01-31 | ナトリックス セパレイションズ インコーポレーテッド | Layered tubular membrane for chromatography and method of use thereof |
ES2622578T3 (en) | 2011-06-10 | 2017-07-06 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
US8815226B2 (en) | 2011-06-10 | 2014-08-26 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
PE20140756A1 (en) | 2011-06-28 | 2014-07-04 | Oxford Biotherapeutics Ltd | ANTIBODIES THAT JOIN BST1 |
ME02632B (en) | 2011-06-28 | 2017-06-20 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
UA117901C2 (en) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Antibody variants and uses thereof |
WO2013022855A1 (en) | 2011-08-05 | 2013-02-14 | Xencor, Inc. | Antibodies with modified isoelectric points and immunofiltering |
US9963481B2 (en) | 2011-09-07 | 2018-05-08 | The Scripps Research Institute | Chiral oligomeric pentenoate amides as bio-oligomer mimetics |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
JP6310394B2 (en) | 2011-10-10 | 2018-04-11 | ゼンコア インコーポレイテッド | Methods for purifying antibodies |
EP2592103A1 (en) | 2011-11-08 | 2013-05-15 | Adriacell S.p.A. | Polymer aldehyde derivatives |
MX350539B (en) | 2012-02-13 | 2017-09-08 | Bristol Myers Squibb Co | Enediyne compounds, conjugates thereof, and uses and methods therefor. |
ES2929759T3 (en) | 2012-04-05 | 2022-12-01 | Nerviano Medical Sciences Srl | New letting agents |
US20150087688A1 (en) * | 2012-04-25 | 2015-03-26 | Ascendis Pharma A/S | Prodrugs of hydroxyl-comprising drugs |
WO2013163631A2 (en) | 2012-04-27 | 2013-10-31 | Cytomx Therapeutics, Inc. | Activatable antibodies that bind epidermal growth factor receptor and methods of use thereof |
AR091649A1 (en) | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | OPTIMIZATION OF ANTIBODIES THAT FIX THE LYMPHOCYTE ACTIVATION GEN 3 (LAG-3) AND ITS USES |
EP3632462A1 (en) | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
US11180572B2 (en) | 2012-07-06 | 2021-11-23 | Genmab B.V. | Dimeric protein with triple mutations |
GB201213652D0 (en) | 2012-08-01 | 2012-09-12 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
SG10201701165TA (en) | 2012-08-14 | 2017-03-30 | Univ Nanyang Tech | Angiopoietin-like 4 antibody and a method of its use in cancer treatment |
US20140161790A1 (en) | 2012-11-19 | 2014-06-12 | Xencor, Inc. | Engineered immunoglobulins with extended in vivo half-life |
US10131682B2 (en) | 2012-11-24 | 2018-11-20 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules |
EP2943506B1 (en) | 2013-01-10 | 2024-03-13 | Genmab B.V. | Human igg1 fc region variants and uses thereof |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
AU2014205086B2 (en) | 2013-01-14 | 2019-04-18 | Xencor, Inc. | Novel heterodimeric proteins |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
EP2945969A1 (en) | 2013-01-15 | 2015-11-25 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
CN103933575B (en) | 2013-01-23 | 2017-09-29 | 上海新理念生物医药科技有限公司 | A kind of three flute profile connexons and its application |
GB201302447D0 (en) | 2013-02-12 | 2013-03-27 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
RS56169B1 (en) | 2013-02-14 | 2017-11-30 | Bristol Myers Squibb Co | Tubulysin compounds, methods of making and use |
US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
CN111138543A (en) | 2013-03-15 | 2020-05-12 | Xencor股份有限公司 | Heterodimeric proteins |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
EP3421495A3 (en) | 2013-03-15 | 2019-05-15 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
EP3049420B1 (en) * | 2013-09-25 | 2019-05-15 | Nerviano Medical Sciences S.r.l. | Thieno[2,3-e]indole derivatives as new antitumor agents |
WO2015050959A1 (en) | 2013-10-01 | 2015-04-09 | Yale University | Anti-kit antibodies and methods of use thereof |
AU2014331714B2 (en) | 2013-10-11 | 2019-05-02 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
PT3055331T (en) | 2013-10-11 | 2021-04-05 | Oxford Bio Therapeutics Ltd | Conjugated antibodies against ly75 for the treatment of cancer |
CN105813655B (en) | 2013-10-11 | 2022-03-15 | 阿萨纳生物科技有限责任公司 | Protein-polymer-drug conjugates |
US9540440B2 (en) | 2013-10-30 | 2017-01-10 | Cytomx Therapeutics, Inc. | Activatable antibodies that bind epidermal growth factor receptor and methods of use thereof |
WO2015089283A1 (en) | 2013-12-11 | 2015-06-18 | Cytomx Therapeutics, Inc. | Antibodies that bind activatable antibodies and methods of use thereof |
SG11201605605SA (en) | 2014-01-10 | 2016-08-30 | Synthon Biopharmaceuticals Bv | Method for purifying cys-linked antibody-drug conjugates |
AU2015205509B2 (en) * | 2014-01-10 | 2019-08-15 | Byondis B.V. | Duocarmycin ADCs showing improved in vivo antitumor activity |
WO2015104373A2 (en) | 2014-01-10 | 2015-07-16 | Synthon Biopharmaceuticals B.V. | Duocarmycin adcs for use in treatment of endometrial cancer |
US10464955B2 (en) | 2014-02-28 | 2019-11-05 | Hangzhou Dac Biotech Co., Ltd. | Charged linkers and their uses for conjugation |
EP3647322B1 (en) | 2014-03-20 | 2021-10-20 | Bristol-Myers Squibb Company | Stabilized fibronectin based scaffold molecules |
EP3954713A3 (en) | 2014-03-28 | 2022-03-30 | Xencor, Inc. | Bispecific antibodies that bind to cd38 and cd3 |
EA037006B1 (en) | 2014-06-06 | 2021-01-26 | Бристол-Майерс Сквибб Компани | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
AU2015286569B2 (en) | 2014-07-11 | 2021-04-15 | Genmab A/S | Antibodies binding AXL |
EP3194449A1 (en) | 2014-07-24 | 2017-07-26 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
US10077287B2 (en) | 2014-11-10 | 2018-09-18 | Bristol-Myers Squibb Company | Tubulysin analogs and methods of making and use |
RS60631B1 (en) | 2014-11-21 | 2020-09-30 | Bristol Myers Squibb Co | Antibodies against cd73 and uses thereof |
EP3221346B1 (en) | 2014-11-21 | 2020-09-02 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
EP3224277B1 (en) | 2014-11-25 | 2020-08-26 | Bristol-Myers Squibb Company | Novel pd-l1 binding polypeptides for imaging |
EP3223866B1 (en) | 2014-11-25 | 2023-03-08 | Bristol-Myers Squibb Company | Methods and compositions for 18f-radiolabeling of the fibronectin type (iii) domain |
CA2967426A1 (en) | 2014-11-26 | 2016-06-02 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and tumor antigens |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
BR112017011166A2 (en) | 2014-11-26 | 2018-02-27 | Xencor, Inc. | heterodimeric antibodies that bind to cd3 and cd38 |
PT3233912T (en) | 2014-12-19 | 2021-08-09 | Regenesance B V | Antibodies that bind human c6 and uses thereof |
WO2016105450A2 (en) | 2014-12-22 | 2016-06-30 | Xencor, Inc. | Trispecific antibodies |
WO2016115201A1 (en) | 2015-01-14 | 2016-07-21 | Bristol-Myers Squibb Company | Heteroarylene-bridged benzodiazepine dimers, conjugates thereof, and methods of making and using |
US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
CN113876962A (en) | 2015-04-07 | 2022-01-04 | 纪念斯隆-凯特琳癌症中心 | Nanoparticle immunoconjugates |
CN106279352B (en) | 2015-05-29 | 2020-05-22 | 上海新理念生物医药科技有限公司 | Derivative of dolastatin 10 and application thereof |
JP6892431B2 (en) | 2015-07-10 | 2021-06-23 | ゲンマブ エー/エス | AXL-Specific Antibodies-Drug Conjugates for Cancer Treatment |
CN113350518A (en) | 2015-07-12 | 2021-09-07 | 杭州多禧生物科技有限公司 | Conjugated bridge linkers to cell binding molecules |
US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
EP3733698A1 (en) | 2015-09-23 | 2020-11-04 | Bristol-Myers Squibb Company | Glypican-3 binding fibronectin based scafflold molecules |
US10618935B2 (en) | 2015-11-03 | 2020-04-14 | Industrial Technology Research Institute | Antibody-drug conjugate (ADC) and method for forming the same |
AU2016356780A1 (en) | 2015-11-19 | 2018-06-28 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof |
CN106729743B (en) | 2015-11-23 | 2021-09-21 | 四川科伦博泰生物医药股份有限公司 | anti-ErbB 2 antibody-drug conjugate, and composition, preparation method and application thereof |
EP3387013B1 (en) | 2015-12-07 | 2022-06-08 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and psma |
EA201891983A8 (en) | 2016-03-04 | 2020-05-28 | Бристол-Майерс Сквибб Компани | COMBINED THERAPY BY ANTIBODIES TO CD73 |
CA3019398A1 (en) | 2016-04-26 | 2017-11-02 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
CN109562195A (en) | 2016-06-01 | 2019-04-02 | 百时美施贵宝公司 | PET imaging is carried out with PD-L1 combination polypeptide |
US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
EP3468997B1 (en) | 2016-06-08 | 2023-09-13 | Xencor, Inc. | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
MX2018015592A (en) | 2016-06-14 | 2019-04-24 | Xencor Inc | Bispecific checkpoint inhibitor antibodies. |
CA3029328A1 (en) | 2016-06-28 | 2018-01-04 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
JP7027401B2 (en) | 2016-07-14 | 2022-03-01 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies to TIM3 and its use |
KR102493853B1 (en) | 2016-08-19 | 2023-01-30 | 브리스톨-마이어스 스큅 컴퍼니 | Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of manufacture and use |
US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
AU2017342559B2 (en) | 2016-10-14 | 2022-03-24 | Xencor, Inc. | Bispecific heterodimeric fusion proteins containing IL-15/IL-15Ralpha Fc-fusion proteins and PD-1 antibody fragments |
WO2018075842A1 (en) | 2016-10-20 | 2018-04-26 | Bristol-Myers Squibb Company | Condensed benzodiazepine derivatives and conjugates made therefrom |
MA46700A (en) | 2016-11-01 | 2021-05-19 | Genmab Bv | POLYPEPTIDIC VARIANTS AND ITS USES |
NZ752394A (en) | 2016-11-14 | 2021-07-30 | Hangzhou Dac Biotech Co Ltd | Conjugation linkers, cell binding molecule-drug conjugates containing the likers, methods of making and uses such conjugates with the linkers |
EP3583124A1 (en) | 2017-02-17 | 2019-12-25 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
CN110621337B (en) | 2017-05-10 | 2021-11-09 | 浙江时迈药业有限公司 | anti-LAG 3 human monoclonal antibodies and uses thereof |
KR20220167342A (en) | 2017-05-25 | 2022-12-20 | 브리스톨-마이어스 스큅 컴퍼니 | Antibodies comprising modified heavy constant regions |
JP2020529832A (en) | 2017-06-30 | 2020-10-15 | ゼンコア インコーポレイテッド | Targeted heterodimer Fc fusion protein containing IL-15 / IL-15Rα and antigen binding domain |
US11566044B2 (en) | 2017-07-26 | 2023-01-31 | The University Of Queensland | Disulfide bond containing compounds and uses thereof |
US10508115B2 (en) | 2017-08-16 | 2019-12-17 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor |
US10494370B2 (en) | 2017-08-16 | 2019-12-03 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor |
US10472361B2 (en) | 2017-08-16 | 2019-11-12 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor |
US10487084B2 (en) | 2017-08-16 | 2019-11-26 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor |
US10457681B2 (en) | 2017-08-16 | 2019-10-29 | Bristol_Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor |
WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | Anti-lap antibodies and uses thereof |
US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
EP3706793A1 (en) | 2017-11-08 | 2020-09-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
CA3084092A1 (en) * | 2017-12-06 | 2019-06-13 | Ontario Institute For Cancer Research (Oicr) | Acyl hydrazone linkers, methods and uses thereof |
WO2019125732A1 (en) | 2017-12-19 | 2019-06-27 | Xencor, Inc. | Engineered il-2 fc fusion proteins |
EP3728273A4 (en) | 2017-12-22 | 2021-12-29 | Ontario Institute for Cancer Research (OICR) | Heterocyclic acyl hydrazone linkers, methods and uses thereof |
JP7358361B2 (en) | 2018-01-12 | 2023-10-10 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies against TIM3 and their uses |
JP2021510740A (en) | 2018-01-24 | 2021-04-30 | ゲンマブ ビー.ブイ. | Polypeptide variants and their uses |
TW202003565A (en) | 2018-03-23 | 2020-01-16 | 美商必治妥美雅史谷比公司 | Antibodies against MICA and/or MICB and uses thereof |
US11155618B2 (en) | 2018-04-02 | 2021-10-26 | Bristol-Myers Squibb Company | Anti-TREM-1 antibodies and uses thereof |
AU2019247415A1 (en) | 2018-04-04 | 2020-10-22 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
CA3097593A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
AU2019256529A1 (en) | 2018-04-18 | 2020-11-26 | Xencor, Inc. | TIM-3 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and TIM-3 antigen binding domains |
US11485741B2 (en) | 2018-04-24 | 2022-11-01 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (TLR7) agonists |
WO2020003210A1 (en) | 2018-06-29 | 2020-01-02 | Kangwon National University University-Industry Cooperation Foundation | Anti-l1cam antibodies and uses thereof |
WO2020010079A2 (en) | 2018-07-02 | 2020-01-09 | Amgen Inc. | Anti-steap1 antigen-binding protein |
US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
JP2022503959A (en) | 2018-10-03 | 2022-01-12 | ゼンコア インコーポレイテッド | IL-12 heterodimer FC-fusion protein |
JP2022504839A (en) | 2018-10-10 | 2022-01-13 | ティロス・セラピューティクス・インコーポレイテッド | Anti-LAP antibody mutants and their use |
JP2022513653A (en) | 2018-11-28 | 2022-02-09 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies containing modified heavy chain constant regions |
WO2020117627A1 (en) | 2018-12-03 | 2020-06-11 | Bristol-Myers Squibb Company | Anti-ido antibody and uses thereof |
CN109762067B (en) | 2019-01-17 | 2020-02-28 | 北京天广实生物技术股份有限公司 | Antibodies that bind human Claudin18.2 and uses thereof |
CA3127236A1 (en) | 2019-01-22 | 2020-07-30 | Bristol-Myers Squibb Company | Antibodies against il-7r alpha subunit and uses thereof |
WO2020180726A1 (en) | 2019-03-01 | 2020-09-10 | Xencor, Inc. | Heterodimeric antibodies that bind enpp3 and cd3 |
WO2021011681A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Antibodies against human trem-1 and uses thereof |
EP3999543A1 (en) | 2019-07-15 | 2022-05-25 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
CN114945409A (en) | 2020-01-13 | 2022-08-26 | 新免疫技术有限公司 | Methods of treating tumors with combinations of IL-7 proteins and bispecific antibodies |
US20230105029A1 (en) | 2020-02-27 | 2023-04-06 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Antibodies binding il4r and uses thereof |
US20230272056A1 (en) | 2020-04-09 | 2023-08-31 | Merck Sharp & Dohme Llc | Affinity matured anti-lap antibodies and uses thereof |
WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
CN114685669A (en) | 2020-12-30 | 2022-07-01 | 和铂医药(苏州)有限公司 | Antibodies that bind TROP2 and uses thereof |
EP4305067A1 (en) | 2021-03-09 | 2024-01-17 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cldn6 |
WO2022192586A1 (en) | 2021-03-10 | 2022-09-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and gpc3 |
EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
Citations (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4169888A (en) * | 1977-10-17 | 1979-10-02 | The Upjohn Company | Composition of matter and process |
EP0154445A1 (en) * | 1984-02-21 | 1985-09-11 | The Upjohn Company | Analogues of antibiotic cc-1065 |
US4671958A (en) * | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
WO1988004659A2 (en) * | 1986-12-19 | 1988-06-30 | The Upjohn Company | Novel cc-1065 analogs |
US4912227A (en) * | 1984-02-21 | 1990-03-27 | The Upjohn Company | 1,2,8,8A-tetrahydrocyclopropa(c)pyrrolo(3,2-e)-indol-4-(5H)-ones and related compounds |
US4923990A (en) * | 1986-04-17 | 1990-05-08 | Kyowa Hakko Kogyo Co., Ltd. | Pyrindamycins A and B and duocarmycin A antibiotics derived from certain streptomyces culture |
US4952394A (en) * | 1987-11-23 | 1990-08-28 | Bristol-Myers Company | Drug-monoclonal antibody conjugates |
US4978757A (en) * | 1984-02-21 | 1990-12-18 | The Upjohn Company | 1,2,8,8a-tetrahydrocyclopropa (C) pyrrolo [3,2-e)]-indol-4(5H)-ones and related compounds |
US4994578A (en) * | 1987-11-27 | 1991-02-19 | Meiji Seika Kaisha, Ltd. | Certain anti-tumor duocarmycin antibiotics from streptomyces |
US5070092A (en) * | 1989-07-03 | 1991-12-03 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives related to dc-88a compound |
US5084468A (en) * | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
US5101038A (en) * | 1988-12-28 | 1992-03-31 | Kyowa Hakko Kogyo Co., Ltd. | Novel substance dc 113 and production thereof |
US5138059A (en) * | 1988-07-22 | 1992-08-11 | Kyowa Hakko Kogyo Co., Ltd. | Dc-89 compounds and process for their preparation |
US5137877A (en) * | 1990-05-14 | 1992-08-11 | Bristol-Myers Squibb | Bifunctional linking compounds, conjugates and methods for their production |
US5187186A (en) * | 1989-07-03 | 1993-02-16 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives |
EP0537575A1 (en) * | 1991-10-07 | 1993-04-21 | Kyowa Hakko Kogyo Co., Ltd. | Hydrobromide of DC-89 derivative having antitumor activity |
US5332837A (en) * | 1986-12-19 | 1994-07-26 | The Upjohn Company | CC-1065 analogs |
US5332740A (en) * | 1990-07-26 | 1994-07-26 | Kyowa Hakko Kogyo Co., Ltd. | DC-89 derivatives |
US5475092A (en) * | 1992-03-25 | 1995-12-12 | Immunogen Inc. | Cell binding agent conjugates of analogues and derivatives of CC-1065 |
EP0689845A2 (en) * | 1994-06-03 | 1996-01-03 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
WO1996010405A1 (en) * | 1994-09-30 | 1996-04-11 | Kyowa Hakko Kogyo Co., Ltd. | Antitumor agent |
US5547667A (en) * | 1990-08-03 | 1996-08-20 | Farmitalia Carlo Erba S.R.L. | Linker for bioactive agents |
US5606017A (en) * | 1992-01-23 | 1997-02-25 | Bristol-Myers Squibb Company | Thioether conjugates |
WO1997012862A1 (en) * | 1995-10-03 | 1997-04-10 | The Scripps Research Institute | Cbi analogs of cc-1065 and the duocarmycins |
US5629430A (en) * | 1992-08-21 | 1997-05-13 | Kyorin Pharmaceutical Co., Ltd. | Trifluoromethylpyrroloindolecarboxylic acid ester and process for production thereof |
US5641780A (en) * | 1994-04-22 | 1997-06-24 | Kyowa Hakko Kogyo Co., Ltd. | Pyrrolo-indole derivatives |
WO1997032850A1 (en) * | 1996-03-08 | 1997-09-12 | The Scripps Research Institute | Mcbi analogs of cc-1065 and the duocarmycins |
WO1997045411A1 (en) * | 1996-05-31 | 1997-12-04 | The Scripps Research Institute | Analogs of cc-1065 and the duocarmycins |
US5703080A (en) * | 1994-05-20 | 1997-12-30 | Kyowa Hakko Kogyo Co., Ltd. | Method for stabilizing duocarmycin derivatives |
US5712374A (en) * | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
US5714586A (en) * | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5739350A (en) * | 1990-04-25 | 1998-04-14 | Pharmacia & Upjohn Company | CC-1065 analogs |
US5773435A (en) * | 1987-08-04 | 1998-06-30 | Bristol-Myers Squibb Company | Prodrugs for β-lactamase and uses thereof |
US5786486A (en) * | 1994-11-29 | 1998-07-28 | Kyorin Pharmaceutical Co., Ltd. | Acrylamide derivatives and process for production thereof |
US5786377A (en) * | 1993-11-19 | 1998-07-28 | Universidad De Santiago De Compostela | Pyrrolo 3,2-E!indol derivatives, process for the preparation thereof and applications |
US6066742A (en) * | 1996-09-18 | 2000-05-23 | Kyorin Pharmaceutical Co., Ltd. | Intermediates for the preparation of duocarmycin SA and derivatives thereof, and process for the production of the intermediates |
US6103236A (en) * | 1995-05-10 | 2000-08-15 | Kyowa Hakko Kogyo Co., Ltd. | Toxin conjugates |
US6143901A (en) * | 1996-07-31 | 2000-11-07 | Genesoft, Inc. | Complex formation between dsDNA and pyrrole imidazole polyamides |
US6194612B1 (en) * | 1995-10-17 | 2001-02-27 | The Scripps Research Institute | Template for solution phase synthesis of combination libraries |
WO2001016324A2 (en) * | 1999-08-31 | 2001-03-08 | Board Of Regents, The University Of Texas System | Methods and compositions of a novel serine protease inhibitor |
US6214345B1 (en) * | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
WO2001049698A1 (en) * | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
US6262271B1 (en) * | 1997-10-14 | 2001-07-17 | The Scripps Research Institute | ISO-CBI and ISO-CI analogs of CC-1065 and the duocarmycins |
US6281354B1 (en) * | 1997-05-22 | 2001-08-28 | The Scripps Research Institute | Analogs of duocarmycin and cc-1065 |
WO2001074898A2 (en) * | 2000-03-16 | 2001-10-11 | Genesoft, Inc. | Charged compounds comprising a nucleic acid binding moiety and uses therefor |
US6310209B1 (en) * | 1997-12-08 | 2001-10-30 | The Scripps Research Institute | Synthesis of CC-1065/duocarmycin analogs |
WO2001083482A1 (en) * | 2000-05-03 | 2001-11-08 | The Scripps Research Institute | Dna alkylating agent and activation thereof |
WO2001085733A1 (en) * | 2000-05-12 | 2001-11-15 | Japan Science And Technology Corporation | Interstrand crosslinking agents for dna and compounds therefor |
US6329497B1 (en) * | 1997-03-28 | 2001-12-11 | The Scripps Research Institute | Sandramycin analogs |
WO2002083180A1 (en) * | 2001-03-23 | 2002-10-24 | Syntarga B.V. | Elongated and multiple spacers in activatible prodrugs |
WO2002088172A2 (en) * | 2001-04-30 | 2002-11-07 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US6512101B1 (en) * | 1995-12-22 | 2003-01-28 | Bristol Myers Squibb Company | Branched hydrazone linkers |
US6534660B1 (en) * | 2002-04-05 | 2003-03-18 | Immunogen, Inc. | CC-1065 analog synthesis |
WO2003022806A2 (en) * | 2001-09-07 | 2003-03-20 | The Scripps Research Institute | Cbi analogues of cc-1065 and the duocarmycins |
US20030073852A1 (en) * | 2001-05-31 | 2003-04-17 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
US6566336B1 (en) * | 1998-09-14 | 2003-05-20 | Japan Science And Technology Corporation | Compounds alkylating specific base sequence of DNA and method for synthesizing the same |
Family Cites Families (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6A (en) * | 1836-08-10 | Thomas blanghard | ||
US4391904A (en) | 1979-12-26 | 1983-07-05 | Syva Company | Test strip kits in immunoassays and compositions therein |
US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
JPS6428264A (en) * | 1987-07-21 | 1989-01-30 | Sumitomo Electric Industries | Production of superconducting material |
US4975278A (en) * | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US5147786A (en) | 1988-04-22 | 1992-09-15 | Monsanto Company | Immunoassay for the detection of α-haloacetamides |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
US5194599A (en) | 1988-09-23 | 1993-03-16 | Gilead Sciences, Inc. | Hydrogen phosphonodithioate compositions |
US4915278A (en) * | 1988-11-03 | 1990-04-10 | Smith Kenneth W | Portable container |
US5176996A (en) | 1988-12-20 | 1993-01-05 | Baylor College Of Medicine | Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
DE3907562A1 (en) | 1989-03-09 | 1990-09-13 | Bayer Ag | ANTISENSE OLIGONUCLEOTIDS FOR INHIBITING THE TRANSACTIVATOR TARGET SEQUENCE (TAR) AND THE SYNTHESIS OF THE TRANSACTIVATOR PROTEIN (TAT) FROM HIV-1 AND THE USE THEREOF |
US5075181A (en) * | 1989-05-05 | 1991-12-24 | Kennametal Inc. | High hardness/high compressive stress multilayer coated tool |
JPH04505261A (en) | 1989-05-10 | 1992-09-17 | スローン―ケツテリング・インステイテユート・フオー・キヤンサー・リサーチ | Stably transformed eukaryotic cells containing transcribable foreign DNA under the control of a Pol III promoter |
KR920701230A (en) | 1989-06-05 | 1992-08-11 | 원본미기재 | Exonuclease-resistant oligonucleotides and methods for preparing the same |
WO1991004753A1 (en) | 1989-10-02 | 1991-04-18 | Cetus Corporation | Conjugates of antisense oligonucleotides and therapeutic uses thereof |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
EP0498843B1 (en) | 1989-10-24 | 1996-06-12 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
US5495009A (en) | 1989-10-24 | 1996-02-27 | Gilead Sciences, Inc. | Oligonucleotide analogs containing thioformacetal linkages |
EP0942000B1 (en) | 1989-10-24 | 2004-06-23 | Isis Pharmaceuticals, Inc. | 2'-Modified oligonucleotides |
US5334528A (en) | 1989-10-30 | 1994-08-02 | The Regents Of The University Of California | Monoclonal antibodies to cyclodiene insecticides and method for detecting the same |
US5180819A (en) | 1989-12-22 | 1993-01-19 | The Trustees Of Columbia University In The City Of New York | Purified myeloblastin, nucleic acid molecule encoding same, and uses thereof |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
DE69120146T2 (en) | 1990-01-12 | 1996-12-12 | Cell Genesys Inc | GENERATION OF XENOGENIC ANTIBODIES |
WO1991011535A1 (en) | 1990-01-30 | 1991-08-08 | Childrens Hospital Of Los Angeles | Inhibition of transcription by double-stranded oligonucleotides |
AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
CA2084987C (en) | 1990-06-11 | 2007-02-13 | Larry Gold | Nucleic acid ligands |
US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
ES2246502T3 (en) | 1990-08-29 | 2006-02-16 | Genpharm International, Inc. | TRANSGENIC NON-HUMAN ANIMALS ABLE TO PRODUCE HETEROLOGICAL ANTIBODIES. |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
CA2092002A1 (en) | 1990-09-20 | 1992-03-21 | Mark Matteucci | Modified internucleoside linkages |
EP0549692A4 (en) | 1990-09-21 | 1993-08-25 | Fred Hutchinson Cancer Research Center | Protein sequence-specific oligonucleotide sequences |
JPH04154298A (en) * | 1990-10-17 | 1992-05-27 | Pioneer Electron Corp | Speaker |
EP0558634A4 (en) | 1990-11-23 | 1995-06-28 | Gilead Sciences Inc | Triplex-forming oligomers containing modified bases |
WO1992010590A1 (en) | 1990-12-10 | 1992-06-25 | Gilead Sciences, Inc. | Inhibition of transcription by formation of triple helixes |
US5840867A (en) | 1991-02-21 | 1998-11-24 | Gilead Sciences, Inc. | Aptamer analogs specific for biomolecules |
WO1992014843A1 (en) | 1991-02-21 | 1992-09-03 | Gilead Sciences, Inc. | Aptamer specific for biomolecules and method of making |
US5582981A (en) | 1991-08-14 | 1996-12-10 | Gilead Sciences, Inc. | Method for identifying an oligonucleotide aptamer specific for a target |
DK1024191T3 (en) | 1991-12-02 | 2008-12-08 | Medical Res Council | Preparation of autoantibodies displayed on phage surfaces from antibody segment libraries |
GB9314960D0 (en) * | 1992-07-23 | 1993-09-01 | Zeneca Ltd | Chemical compounds |
US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
US5324483B1 (en) | 1992-10-08 | 1996-09-24 | Warner Lambert Co | Apparatus for multiple simultaneous synthesis |
DE4314091A1 (en) | 1993-04-29 | 1994-11-03 | Boehringer Mannheim Gmbh | Immunological detection method for triazines |
US5502037A (en) * | 1993-07-09 | 1996-03-26 | Neuromed Technologies, Inc. | Pro-cytotoxic drug conjugates for anticancer therapy |
US5773011A (en) | 1993-09-27 | 1998-06-30 | Gerbu Biotechnik Gmbh | Method of preparing a synergistic immunological adjuvant formulation |
DE4410559A1 (en) * | 1994-03-26 | 1995-09-28 | Hoechst Ag | Oriented polyolefin film with amorphous polymer, process for its production and its use |
EP0769967B1 (en) * | 1994-08-19 | 2007-12-12 | La Region Wallonne | Conjugates comprising an antitumour agent and their use |
US5580089A (en) * | 1994-10-11 | 1996-12-03 | Kolka; David B. | Vehicle stabilization system and method |
US5846645A (en) * | 1995-03-03 | 1998-12-08 | Asahi Glass Company Ltd. | Fluorocarbon resin-coated product |
US5686237A (en) | 1995-06-05 | 1997-11-11 | Al-Bayati; Mohammed A. S. | Use of biomarkers in saliva to evaluate the toxicity of agents and the function of tissues in both biomedical and environmental applications |
US5646298A (en) * | 1995-06-07 | 1997-07-08 | Procoron, Inc. | Cyclopropylindole prodrugs |
US5545805A (en) * | 1995-06-07 | 1996-08-13 | Chesner Engineering, Pc | Enhanced stabilization of lead in solid residues using acid oxyanion and alkali-metal carbonate treatment |
US5769650A (en) * | 1995-06-19 | 1998-06-23 | Sumitomo Wiring Systems, Ltd. | Connector and cover therefor |
US5760072A (en) * | 1995-12-29 | 1998-06-02 | Pharmachemie B.V. | Paclitaxel prodrugs, method for preparation as well as their use in selective chemotherapy |
US5685237A (en) * | 1996-01-16 | 1997-11-11 | David Lehrman | Extendable support foot for an ironing board |
US5843937A (en) * | 1996-05-23 | 1998-12-01 | Panorama Research, Inc. | DNA-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents |
WO1998009966A1 (en) * | 1996-09-03 | 1998-03-12 | Kyowa Hakko Kogyo Co., Ltd. | Dc-89 derivatives |
US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
US6759509B1 (en) | 1996-11-05 | 2004-07-06 | Bristol-Myers Squibb Company | Branched peptide linkers |
WO1998025900A1 (en) | 1996-12-13 | 1998-06-18 | Shionogi & Co., Ltd. | Compounds having antitumor activity |
WO1998050432A1 (en) * | 1997-05-07 | 1998-11-12 | Bristol-Myers Squibb Company | Recombinant antibody-enzyme fusion proteins |
US6316522B1 (en) | 1997-08-18 | 2001-11-13 | Scimed Life Systems, Inc. | Bioresorbable hydrogel compositions for implantable prostheses |
US7425541B2 (en) | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
DK1144011T3 (en) | 1998-12-11 | 2010-07-05 | Coulter Pharm Inc | Pro-drug compounds and processes for their preparation |
DE10008089A1 (en) | 2000-02-22 | 2001-10-31 | Biotechnolog Forschung Gmbh | Production of tubulysin compounds comprises multi-stage process including condensation of N-methylpipecolinoyl-isoleucine with substituted thiazole-4-carboxylic acid derivative |
AU7552501A (en) | 2000-06-14 | 2002-01-08 | Corixa Corp | Tripeptide prodrug compounds |
WO2001095943A2 (en) | 2000-06-14 | 2001-12-20 | Medarex, Inc. | Prodrug compounds with an oligopeptide having an isoleucine residue |
EP1294405A2 (en) | 2000-06-14 | 2003-03-26 | Corixa Corporation | Prodrug compounds cleavable by thimet oligopeptidase |
US7402556B2 (en) | 2000-08-24 | 2008-07-22 | Medarex, Inc. | Prodrugs activated by plasmin and their use in cancer chemotherapy |
US20030083263A1 (en) | 2001-04-30 | 2003-05-01 | Svetlana Doronina | Pentapeptide compounds and uses related thereto |
US7256257B2 (en) | 2001-04-30 | 2007-08-14 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
MXPA03010961A (en) | 2001-05-31 | 2004-02-27 | Vertex Pharma | Thiazole compounds useful as inhibitors of protein kinases. |
EP1404356B1 (en) | 2001-06-11 | 2011-04-06 | Medarex, Inc. | Method for designing cd10-activated prodrug compounds |
US7091186B2 (en) * | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
WO2003043583A2 (en) | 2001-11-20 | 2003-05-30 | Seattle Genetics, Inc. | Treatment of immunological disorders using anti-cd30 antibodies |
TW557623B (en) * | 2001-11-28 | 2003-10-11 | Ind Tech Res Inst | Integrated demodulator for single-phase input frequency modulation signal |
US6756397B2 (en) * | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
US7816377B2 (en) | 2002-07-09 | 2010-10-19 | R&D-Biopharmaceuticals Gmbh | Tubulysin analogues |
EP1521769B1 (en) | 2002-07-09 | 2015-09-09 | Dömling, Alexander | Tubulysin conjugates |
US20050180972A1 (en) | 2002-07-31 | 2005-08-18 | Wahl Alan F. | Anti-CD20 antibody-drug conjugates for the treatment of cancer and immune disorders |
JP5356648B2 (en) | 2003-02-20 | 2013-12-04 | シアトル ジェネティックス, インコーポレイテッド | Anti-CD70 antibody-drug conjugates and their use for the treatment of cancer and immune disorders |
WO2004101767A2 (en) | 2003-05-13 | 2004-11-25 | The Scripps Research Institute | Cbi analogues of the duocarmycins and cc-1065 |
EP1747021B1 (en) | 2004-05-19 | 2015-09-09 | E. R. Squibb & Sons, L.L.C. | Self-immolative linkers and drug conjugates |
US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
US7180819B1 (en) | 2005-10-04 | 2007-02-20 | Lsi Logic Corporation | Converting dual port memory into 2 single port memories |
RU2489423C2 (en) | 2006-02-02 | 2013-08-10 | Синтарга Б.В. | Water-soluble analogues cc-1065 and their conjugates |
-
2002
- 2002-05-31 US US10/160,972 patent/US7129261B2/en not_active Expired - Lifetime
- 2002-05-31 CN CN200910173556A patent/CN101671335A/en active Pending
- 2002-05-31 EP EP02731994A patent/EP1434778A4/en not_active Withdrawn
- 2002-05-31 EP EP10178144A patent/EP2266986A1/en not_active Withdrawn
- 2002-05-31 CN CN02802159A patent/CN1463270A/en active Pending
- 2002-05-31 KR KR10-2003-7001398A patent/KR20030033007A/en active Search and Examination
- 2002-05-31 NZ NZ529788A patent/NZ529788A/en not_active IP Right Cessation
- 2002-05-31 AU AU2002303929A patent/AU2002303929B9/en not_active Ceased
- 2002-05-31 US US10/161,234 patent/US7087600B2/en not_active Ceased
- 2002-05-31 JP JP2003500089A patent/JP4961095B2/en not_active Expired - Lifetime
- 2002-05-31 MX MXPA03011094A patent/MXPA03011094A/en active IP Right Grant
- 2002-05-31 US US10/161,233 patent/US6989452B2/en not_active Expired - Lifetime
- 2002-05-31 WO PCT/US2002/017210 patent/WO2002096910A1/en active Application Filing
- 2002-05-31 CA CA2448319A patent/CA2448319C/en not_active Expired - Fee Related
- 2002-05-31 IL IL15418302A patent/IL154183A0/en unknown
-
2003
- 2003-01-29 IL IL154183A patent/IL154183A/en not_active IP Right Cessation
-
2005
- 2005-06-21 US US11/133,970 patent/US7498302B2/en not_active Expired - Lifetime
- 2005-09-12 US US11/224,580 patent/US7507420B2/en not_active Expired - Lifetime
-
2008
- 2008-05-23 US US12/126,731 patent/USRE41252E1/en not_active Expired - Lifetime
-
2009
- 2009-03-02 US US12/396,266 patent/US8034959B2/en not_active Expired - Fee Related
- 2009-03-04 US US12/397,834 patent/US7977465B2/en not_active Expired - Fee Related
- 2009-04-07 JP JP2009092549A patent/JP2009155342A/en active Pending
Patent Citations (72)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4169888A (en) * | 1977-10-17 | 1979-10-02 | The Upjohn Company | Composition of matter and process |
US4671958A (en) * | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
EP0154445A1 (en) * | 1984-02-21 | 1985-09-11 | The Upjohn Company | Analogues of antibiotic cc-1065 |
US4912227A (en) * | 1984-02-21 | 1990-03-27 | The Upjohn Company | 1,2,8,8A-tetrahydrocyclopropa(c)pyrrolo(3,2-e)-indol-4-(5H)-ones and related compounds |
US4978757A (en) * | 1984-02-21 | 1990-12-18 | The Upjohn Company | 1,2,8,8a-tetrahydrocyclopropa (C) pyrrolo [3,2-e)]-indol-4(5H)-ones and related compounds |
US4923990A (en) * | 1986-04-17 | 1990-05-08 | Kyowa Hakko Kogyo Co., Ltd. | Pyrindamycins A and B and duocarmycin A antibiotics derived from certain streptomyces culture |
WO1988004659A2 (en) * | 1986-12-19 | 1988-06-30 | The Upjohn Company | Novel cc-1065 analogs |
US5332837A (en) * | 1986-12-19 | 1994-07-26 | The Upjohn Company | CC-1065 analogs |
US5773435A (en) * | 1987-08-04 | 1998-06-30 | Bristol-Myers Squibb Company | Prodrugs for β-lactamase and uses thereof |
US4952394A (en) * | 1987-11-23 | 1990-08-28 | Bristol-Myers Company | Drug-monoclonal antibody conjugates |
US4994578A (en) * | 1987-11-27 | 1991-02-19 | Meiji Seika Kaisha, Ltd. | Certain anti-tumor duocarmycin antibiotics from streptomyces |
US5037993A (en) * | 1987-11-27 | 1991-08-06 | Meiji Seika Kaisha Ltd. | Sulfonyl derivatives of an antibiotic substance isolated from streptomyces |
US5138059A (en) * | 1988-07-22 | 1992-08-11 | Kyowa Hakko Kogyo Co., Ltd. | Dc-89 compounds and process for their preparation |
US5084468A (en) * | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
US5117006A (en) * | 1988-08-11 | 1992-05-26 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives useful as antitumor agents |
US5101038A (en) * | 1988-12-28 | 1992-03-31 | Kyowa Hakko Kogyo Co., Ltd. | Novel substance dc 113 and production thereof |
US5187186A (en) * | 1989-07-03 | 1993-02-16 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives |
US5070092A (en) * | 1989-07-03 | 1991-12-03 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives related to dc-88a compound |
US5739350A (en) * | 1990-04-25 | 1998-04-14 | Pharmacia & Upjohn Company | CC-1065 analogs |
US5137877B1 (en) * | 1990-05-14 | 1996-01-30 | Bristol Myers Squibb Co | Bifunctional linking compounds conjugates and methods for their production |
US5137877A (en) * | 1990-05-14 | 1992-08-11 | Bristol-Myers Squibb | Bifunctional linking compounds, conjugates and methods for their production |
US5332740A (en) * | 1990-07-26 | 1994-07-26 | Kyowa Hakko Kogyo Co., Ltd. | DC-89 derivatives |
US5547667A (en) * | 1990-08-03 | 1996-08-20 | Farmitalia Carlo Erba S.R.L. | Linker for bioactive agents |
EP0537575A1 (en) * | 1991-10-07 | 1993-04-21 | Kyowa Hakko Kogyo Co., Ltd. | Hydrobromide of DC-89 derivative having antitumor activity |
US5606017A (en) * | 1992-01-23 | 1997-02-25 | Bristol-Myers Squibb Company | Thioether conjugates |
US5622929A (en) * | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
US5475092A (en) * | 1992-03-25 | 1995-12-12 | Immunogen Inc. | Cell binding agent conjugates of analogues and derivatives of CC-1065 |
US5846545A (en) * | 1992-03-25 | 1998-12-08 | Immunogen, Inc. | Targeted delivery of cyclopropylbenzindole-containing cytotoxic drugs |
US5585499A (en) * | 1992-03-25 | 1996-12-17 | Immunogen Inc. | Cyclopropylbenzindole-containing cytotoxic drugs |
US5629430A (en) * | 1992-08-21 | 1997-05-13 | Kyorin Pharmaceutical Co., Ltd. | Trifluoromethylpyrroloindolecarboxylic acid ester and process for production thereof |
US6214345B1 (en) * | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
US5786377A (en) * | 1993-11-19 | 1998-07-28 | Universidad De Santiago De Compostela | Pyrrolo 3,2-E!indol derivatives, process for the preparation thereof and applications |
US5641780A (en) * | 1994-04-22 | 1997-06-24 | Kyowa Hakko Kogyo Co., Ltd. | Pyrrolo-indole derivatives |
US5703080A (en) * | 1994-05-20 | 1997-12-30 | Kyowa Hakko Kogyo Co., Ltd. | Method for stabilizing duocarmycin derivatives |
US5773001A (en) * | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
EP0689845A2 (en) * | 1994-06-03 | 1996-01-03 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5877296A (en) * | 1994-06-03 | 1999-03-02 | American Cyanamid Company | Process for preparing conjugates of methyltrithio antitumor agents |
WO1996010405A1 (en) * | 1994-09-30 | 1996-04-11 | Kyowa Hakko Kogyo Co., Ltd. | Antitumor agent |
US5786486A (en) * | 1994-11-29 | 1998-07-28 | Kyorin Pharmaceutical Co., Ltd. | Acrylamide derivatives and process for production thereof |
US6103236A (en) * | 1995-05-10 | 2000-08-15 | Kyowa Hakko Kogyo Co., Ltd. | Toxin conjugates |
US5714586A (en) * | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) * | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
WO1997012862A1 (en) * | 1995-10-03 | 1997-04-10 | The Scripps Research Institute | Cbi analogs of cc-1065 and the duocarmycins |
US6548530B1 (en) * | 1995-10-03 | 2003-04-15 | The Scripps Research Institute | CBI analogs of CC-1065 and the duocarmycins |
US6194612B1 (en) * | 1995-10-17 | 2001-02-27 | The Scripps Research Institute | Template for solution phase synthesis of combination libraries |
US6512101B1 (en) * | 1995-12-22 | 2003-01-28 | Bristol Myers Squibb Company | Branched hydrazone linkers |
WO1997032850A1 (en) * | 1996-03-08 | 1997-09-12 | The Scripps Research Institute | Mcbi analogs of cc-1065 and the duocarmycins |
US5985908A (en) * | 1996-03-08 | 1999-11-16 | The Scripps Research Institute | MCBI analogs of CC-1065 and the duocarmycins |
US6060608A (en) * | 1996-05-31 | 2000-05-09 | The Scripps Research Institute | Analogs of CC-1065 and the duocarmycins |
WO1997045411A1 (en) * | 1996-05-31 | 1997-12-04 | The Scripps Research Institute | Analogs of cc-1065 and the duocarmycins |
US6143901A (en) * | 1996-07-31 | 2000-11-07 | Genesoft, Inc. | Complex formation between dsDNA and pyrrole imidazole polyamides |
US6066742A (en) * | 1996-09-18 | 2000-05-23 | Kyorin Pharmaceutical Co., Ltd. | Intermediates for the preparation of duocarmycin SA and derivatives thereof, and process for the production of the intermediates |
US6329497B1 (en) * | 1997-03-28 | 2001-12-11 | The Scripps Research Institute | Sandramycin analogs |
US6281354B1 (en) * | 1997-05-22 | 2001-08-28 | The Scripps Research Institute | Analogs of duocarmycin and cc-1065 |
US6262271B1 (en) * | 1997-10-14 | 2001-07-17 | The Scripps Research Institute | ISO-CBI and ISO-CI analogs of CC-1065 and the duocarmycins |
US6486326B2 (en) * | 1997-10-14 | 2002-11-26 | The Scripps Research Institute | iso-CBI and iso-CI analogs of CC-1065 duocarmycins |
US6310209B1 (en) * | 1997-12-08 | 2001-10-30 | The Scripps Research Institute | Synthesis of CC-1065/duocarmycin analogs |
US6566336B1 (en) * | 1998-09-14 | 2003-05-20 | Japan Science And Technology Corporation | Compounds alkylating specific base sequence of DNA and method for synthesizing the same |
WO2001016324A2 (en) * | 1999-08-31 | 2001-03-08 | Board Of Regents, The University Of Texas System | Methods and compositions of a novel serine protease inhibitor |
WO2001049698A1 (en) * | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
WO2001074898A2 (en) * | 2000-03-16 | 2001-10-11 | Genesoft, Inc. | Charged compounds comprising a nucleic acid binding moiety and uses therefor |
US6555693B2 (en) * | 2000-03-16 | 2003-04-29 | Genesoft, Inc. | Charged compounds comprising a nucleic acid binding moiety and uses therefor |
WO2001083482A1 (en) * | 2000-05-03 | 2001-11-08 | The Scripps Research Institute | Dna alkylating agent and activation thereof |
WO2001085733A1 (en) * | 2000-05-12 | 2001-11-15 | Japan Science And Technology Corporation | Interstrand crosslinking agents for dna and compounds therefor |
WO2002083180A1 (en) * | 2001-03-23 | 2002-10-24 | Syntarga B.V. | Elongated and multiple spacers in activatible prodrugs |
WO2002088172A2 (en) * | 2001-04-30 | 2002-11-07 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US20030073852A1 (en) * | 2001-05-31 | 2003-04-17 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
US6989452B2 (en) * | 2001-05-31 | 2006-01-24 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
US7129261B2 (en) * | 2001-05-31 | 2006-10-31 | Medarex, Inc. | Cytotoxic agents |
WO2003022806A2 (en) * | 2001-09-07 | 2003-03-20 | The Scripps Research Institute | Cbi analogues of cc-1065 and the duocarmycins |
US6534660B1 (en) * | 2002-04-05 | 2003-03-18 | Immunogen, Inc. | CC-1065 analog synthesis |
US6586618B1 (en) * | 2002-04-05 | 2003-07-01 | Immunogen Inc. | CC-1065 analog synthesis |
Non-Patent Citations (23)
Title |
---|
1,2,9,9a-Tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) Analogs of CC-1065 and the Duocarmycins: Synthesis and Evaluation, Dale L. Boger, Biorganic & Medicinal Chemistry, vol. 3, No. 11, pp. 1429 1453, 1995. * |
Antitumor Antibiotics: Duocarmycins, Satoru Nagamura, Chemistry of Heterocyclic Compounds, vol. 34, No. 12, 1998. * |
CC-1065 and the Duocarmycins: Synthetic Studies, Dale L. Boger, Chemical Review, vol. 97, No. 3, pp. 787-828. * |
CC-1065 and the Duocarmycins: Understanding their Biological Function through Mechanistic Studies, Dale L. Boger, Chem. Int. Ed. Engl. 1996, 35, 1438-1474. * |
Colella et al., Mistmatch repair deficiency is associated with resistance to DNA minor groove alkylating agents. British Journal of Cancer. 1999. vol. 80. No. 3/4. pp. 338-343.* * |
Cytotoxicity and Antitumor Activity of Carzelesin, A Prodrug Cyclopropylpyrroloindole Analogue1, L.H. Li, Cancer Research 52, 4904-4913, Sep. 15, 1992. * |
Dissecting the Complex Structure of CC-1065, Martha A. Warpehoski, Drugs of the Future 1991, 16(2) 131-141. * |
Duocarmycin SA Shortened, Simplified, and Extended Agents: A Systematic Examination of the Role of the DNA Binding Subunit, Dale L. Boger, J. Am. Chem. Soc., vol. 119, No. 21, 1997 4979. * |
Enhancement of the Selectivity and Antitumor Efficacy of a CC-1065 Analogue through Immunoconjugate Formation, Ravi V. J. Chari, Cancer Research, 55, 4079-4084, Sep. 15, 1995. * |
International Search Report, issued in International Application No. PCT/US02/17210. * |
Novel Synthesis of Optically Active CC-1065, U-73,975 (Adozelesin), U-80,244 (Carzelesin), U-77,779 (Bizelesin), KW-2189 and DU-861, Yasumichi Fukuda, Heterocycles, vol. 45, No. 12, 1997. * |
Preparation and In Vitro Cytotoxicity of a Methotrexate-Anti-MM46 Monoclonal Antibody Conjugate Via An Oligopeptide Spacer, Naoji Umemoto, Int. J. Cancer: 43, 677-684 (1989). * |
Snythesis and Biological Evaluation of 2′-Carbamate—Linked and 2′-Carbonate—Linked Prodrugs of Paclitaxel: Selective Activation by the Tumor—Associated Protease Plasmin, Franciscus M.H. de Groot, J. Med. Chem. 2000, 43, 3093-3102. * |
Snythesis and Biological Evaluation of 2'-Carbamate-Linked and 2'-Carbonate-Linked Prodrugs of Paclitaxel: Selective Activation by the Tumor-Associated Protease Plasmin, Franciscus M.H. de Groot, J. Med. Chem. 2000, 43, 3093-3102. * |
Stereoelectronic Factors Influencing the Biological Activity and DNA Interaction of Synthetic Antitumor Agents Modeled on CC-1065, M.A. Warpehoski, J. Med. Chem 1988, 31, 590-603. * |
Structure-Activity Relationships of (+)-CC-1065 Analogues in the Inhibition of Helicase-Catalyzed Unwinding of Duplex DNA, Daekyu Sun, Journal of Medicinal Chemistry, 1992, vol. 35, No. 10. * |
Structure—Activity Relationships of (+)-CC-1065 Analogues in the Inhibition of Helicase—Catalyzed Unwinding of Duplex DNA, Daekyu Sun, Journal of Medicinal Chemistry, 1992, vol. 35, No. 10. * |
Synthesis and Antitumor Activity of Duocarmycin Derivatives, Satoru Nagamura, Chem. Pharm. Bull, 43(9) 1530-1535 (1995). * |
Synthesis and Antitumor Activity of Duocarmycin Derivatives: Modification of Segment A of Duocarmycin B2, Satoru Nagamura, 1996 Pharmaceutical Society of Japan. * |
Synthesis and Biochemical Evaluation of the CBI-PDE-I-dimer, a Benzannelated Analog of (+)-CC-1065 That Also Produces Delayed Toxicity in Mice, Paul A. Aristoff, J. Med. Chem. 1993, 36, 1956-1963. * |
Synthesis and Preliminary Evaluation of (+)-CC-Indole2: An Enhanced Functional Analog (+)-CC-1065, Dale L. Boger, Inorganic & Medicinal Chemistry Letters, vol. 1, No. 2, pp. 115-120, 1991. * |
Synthesis of N-(tert-Butyloxycarbonyl)-CBI, CBI, CBI-CDPI and CBI-CDPI2: Enhanced Functional Analogues of CC-1065 Incorporating the 1,2,9,9a-Tetrahydrocyclopropa[c]benz[e]indo-4-one (CBI) Left-Hand Subunit, Dale L. Boger, Angew. J. Org. Chem, 1990, 55, 5823-5832. * |
Synthesis, Chemical Properties, and Preliminary Evaluation of Substituted CBI Analogs of CC-1065 and the Duocarmycins . . . , Dale L. Boger, J. Org. Chem. 1996, 61, 4894-4912. * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012162482A1 (en) | 2011-05-26 | 2012-11-29 | Bristol-Myers Squibb Company | Immunoconjugates, compositions containing them, and methods of making and use |
US8852599B2 (en) | 2011-05-26 | 2014-10-07 | Bristol-Myers Squibb Company | Immunoconjugates, compositions for making them, and methods of making and use |
US9186416B2 (en) | 2011-05-26 | 2015-11-17 | Bristol-Myers Squibb Company | Immunoconjugates, compositions for making them, and methods of making and use |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
USRE41252E1 (en) | Peptidyl prodrugs and linkers and stabilizers useful therefor | |
ZA200300735B (en) | Cytotoxins, prodrugs, linkers and stabilizers useful therefor. | |
US8399403B2 (en) | Chemical linkers and conjugates thereof | |
EP1747021B1 (en) | Self-immolative linkers and drug conjugates | |
EP1940470B1 (en) | Antibody-drug conjugates and their use | |
US8461117B2 (en) | Chemical linkers and cleavable substrates and conjugates thereof | |
US8664407B2 (en) | Chemical linkers with single amino acids and conjugates thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: MEDAREX, INC., NEW JERSEY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NG, HOWARD P.;MCGEE, DANNY P.C.;WU, GUOXIAN;AND OTHERS;SIGNING DATES FROM 20020808 TO 20021008;REEL/FRAME:024369/0785 Owner name: MEDAREX, INC.,NEW JERSEY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NG, HOWARD P.;MCGEE, DANNY P.C.;WU, GUOXIAN;AND OTHERS;SIGNING DATES FROM 20020808 TO 20021008;REEL/FRAME:024369/0785 |
|
AS | Assignment |
Owner name: MEDAREX, INC.,NEW JERSEY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MARTICHONOK, VALERI;REEL/FRAME:024397/0841 Effective date: 20080213 |
|
AS | Assignment |
Owner name: MEDAREX, L.L.C., NEW JERSEY Free format text: MERGER;ASSIGNOR:MEDAREX, INC.;REEL/FRAME:030603/0924 Effective date: 20121231 |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
AS | Assignment |
Owner name: E. R. SQUIBB & SONS, L.L.C., NEW JERSEY Free format text: MERGER;ASSIGNOR:MEDAREX, L.L.C.;REEL/FRAME:035226/0690 Effective date: 20140930 |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 12TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1553) Year of fee payment: 12 |