JP2013506709A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2013506709A5 JP2013506709A5 JP2012533123A JP2012533123A JP2013506709A5 JP 2013506709 A5 JP2013506709 A5 JP 2013506709A5 JP 2012533123 A JP2012533123 A JP 2012533123A JP 2012533123 A JP2012533123 A JP 2012533123A JP 2013506709 A5 JP2013506709 A5 JP 2013506709A5
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- maytansinoid
- peg
- conjugate
- linked
- 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.)
- Pending
Links
- 239000000562 conjugate Substances 0.000 description 237
- 210000004027 cell Anatomy 0.000 description 214
- 229920001223 polyethylene glycol Polymers 0.000 description 155
- 239000003814 drug Substances 0.000 description 126
- 229940079593 drug Drugs 0.000 description 122
- 239000002202 Polyethylene glycol Substances 0.000 description 112
- 239000011230 binding agent Substances 0.000 description 112
- 238000006243 chemical reaction Methods 0.000 description 105
- 229960005558 mertansine Drugs 0.000 description 99
- 125000005647 linker group Chemical group 0.000 description 79
- 230000021615 conjugation Effects 0.000 description 75
- -1 succinimidyl Chemical group 0.000 description 67
- 150000001875 compounds Chemical class 0.000 description 59
- 238000000034 method Methods 0.000 description 57
- 150000003568 thioethers Chemical group 0.000 description 54
- 206010028980 Neoplasm Diseases 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- ANZJBCHSOXCCRQ-FKUXLPTCSA-N mertansine Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCS)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ANZJBCHSOXCCRQ-FKUXLPTCSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 46
- 239000000427 antigen Substances 0.000 description 39
- 102000036639 antigens Human genes 0.000 description 39
- 108091007433 antigens Proteins 0.000 description 39
- 125000004432 carbon atom Chemical group C* 0.000 description 39
- 125000003396 thiol group Chemical group [H]S* 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 125000003118 aryl group Chemical group 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 125000000623 heterocyclic group Chemical group 0.000 description 29
- 201000011510 cancer Diseases 0.000 description 28
- 239000003153 chemical reaction reagent Substances 0.000 description 28
- 150000002148 esters Chemical class 0.000 description 28
- 125000006850 spacer group Chemical group 0.000 description 28
- 230000027455 binding Effects 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 26
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 25
- 229940127089 cytotoxic agent Drugs 0.000 description 25
- 239000004971 Cross linker Substances 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 150000001412 amines Chemical class 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 125000001931 aliphatic group Chemical group 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 125000003342 alkenyl group Chemical group 0.000 description 21
- 125000000304 alkynyl group Chemical group 0.000 description 21
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 19
- 239000002254 cytotoxic agent Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 238000011282 treatment Methods 0.000 description 19
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000003960 organic solvent Substances 0.000 description 18
- 239000000872 buffer Substances 0.000 description 17
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 16
- 230000001472 cytotoxic effect Effects 0.000 description 16
- 229940127121 immunoconjugate Drugs 0.000 description 16
- 239000000178 monomer Substances 0.000 description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- 231100000433 cytotoxic Toxicity 0.000 description 15
- 230000003013 cytotoxicity Effects 0.000 description 15
- 231100000135 cytotoxicity Toxicity 0.000 description 15
- 125000000524 functional group Chemical group 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 239000003431 cross linking reagent Substances 0.000 description 14
- 125000006165 cyclic alkyl group Chemical group 0.000 description 14
- 238000001819 mass spectrum Methods 0.000 description 14
- 238000001556 precipitation Methods 0.000 description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 14
- IADUWZMNTKHTIN-MLSWMBHTSA-N (2,5-dioxopyrrolidin-1-yl) 4-[[3-[3-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]methyl]cyclohexane-1-carboxylate Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)[C@H](C)N(C)C(=O)CCSC2CC(=O)N(CC3CCC(CC3)C(=O)ON3C(=O)CCC3=O)C2=O)[C@]2(C)O[C@H]2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 IADUWZMNTKHTIN-MLSWMBHTSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 238000011068 loading method Methods 0.000 description 13
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000002523 gelfiltration Methods 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 11
- 229930126263 Maytansine Natural products 0.000 description 11
- 231100000599 cytotoxic agent Toxicity 0.000 description 11
- 210000002381 plasma Anatomy 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000012062 aqueous buffer Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 238000004949 mass spectrometry Methods 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- JSHOVKSMJRQOGY-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCSSC1=CC=CC=N1 JSHOVKSMJRQOGY-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 9
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- NKUZQMZWTZAPSN-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-bromoacetate Chemical compound BrCC(=O)ON1C(=O)CCC1=O NKUZQMZWTZAPSN-UHFFFAOYSA-N 0.000 description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- 206010009944 Colon cancer Diseases 0.000 description 8
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 8
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 8
- 108020004459 Small interfering RNA Proteins 0.000 description 8
- 108010000499 Thromboplastin Proteins 0.000 description 8
- 102000002262 Thromboplastin Human genes 0.000 description 8
- 150000001793 charged compounds Chemical class 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 102000006495 integrins Human genes 0.000 description 8
- 108010044426 integrins Proteins 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 208000029742 colonic neoplasm Diseases 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 229910000160 potassium phosphate Inorganic materials 0.000 description 7
- 235000011009 potassium phosphates Nutrition 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 6
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 6
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 6
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 6
- 102100025390 Integrin beta-2 Human genes 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229920013746 hydrophilic polyethylene oxide Polymers 0.000 description 6
- 230000005917 in vivo anti-tumor Effects 0.000 description 6
- 238000010348 incorporation Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 5
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 5
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 5
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 5
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 5
- 102100035721 Syndecan-1 Human genes 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 230000001588 bifunctional effect Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 125000002228 disulfide group Chemical group 0.000 description 5
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- VRDGQQTWSGDXCU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-iodoacetate Chemical compound ICC(=O)ON1C(=O)CCC1=O VRDGQQTWSGDXCU-UHFFFAOYSA-N 0.000 description 4
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 4
- WGMMKWFUXPMTRW-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[(2-bromoacetyl)amino]propanoate Chemical compound BrCC(=O)NCCC(=O)ON1C(=O)CCC1=O WGMMKWFUXPMTRW-UHFFFAOYSA-N 0.000 description 4
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 4
- GTBCXYYVWHFQRS-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)pentanoate Chemical compound C=1C=CC=NC=1SSC(C)CCC(=O)ON1C(=O)CCC1=O GTBCXYYVWHFQRS-UHFFFAOYSA-N 0.000 description 4
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 102100027207 CD27 antigen Human genes 0.000 description 4
- 101150013553 CD40 gene Proteins 0.000 description 4
- 102100032912 CD44 antigen Human genes 0.000 description 4
- 102100025221 CD70 antigen Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 4
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 4
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 4
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 4
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 4
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 4
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 4
- 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 4
- 108091006905 Human Serum Albumin Proteins 0.000 description 4
- 102000008100 Human Serum Albumin Human genes 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 4
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 4
- 108010063738 Interleukins Proteins 0.000 description 4
- 102000015696 Interleukins Human genes 0.000 description 4
- 208000034578 Multiple myelomas Diseases 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 4
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 4
- 229920005654 Sephadex Polymers 0.000 description 4
- 239000012507 Sephadex™ Substances 0.000 description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 4
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
- 108010044540 auristatin Proteins 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 125000003636 chemical group Chemical group 0.000 description 4
- 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 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000005179 haloacetyl group Chemical group 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 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 4
- 238000004519 manufacturing process Methods 0.000 description 4
- SVVGCFZPFZGWRG-OTKBOCOUSA-N maytansinoid dm4 Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)C(C)(C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 SVVGCFZPFZGWRG-OTKBOCOUSA-N 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XQUPVDVFXZDTLT-UHFFFAOYSA-N 1-[4-[[4-(2,5-dioxopyrrol-1-yl)phenyl]methyl]phenyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C=C1)=CC=C1CC1=CC=C(N2C(C=CC2=O)=O)C=C1 XQUPVDVFXZDTLT-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- YOJQJVOLXIGESQ-UHFFFAOYSA-N 3-[2-[2-[2-[2-(pyridin-2-yldisulfanyl)ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid Chemical compound OC(=O)CCOCCOCCOCCOCCSSC1=CC=CC=N1 YOJQJVOLXIGESQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 3
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 3
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 208000012766 Growth delay Diseases 0.000 description 3
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 3
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 3
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 3
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 3
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 3
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 3
- 102100034256 Mucin-1 Human genes 0.000 description 3
- 102100023123 Mucin-16 Human genes 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101800004937 Protein C Proteins 0.000 description 3
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 3
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 3
- 102400000827 Saposin-D Human genes 0.000 description 3
- 101800001700 Saposin-D Proteins 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 3
- 229930195731 calicheamicin Natural products 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003118 drug derivative Substances 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229920003192 poly(bis maleimide) Polymers 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 230000004845 protein aggregation Effects 0.000 description 3
- 229960000856 protein c Drugs 0.000 description 3
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical class 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 3
- 239000002994 raw material Substances 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 2
- OJQSISYVGFJJBY-UHFFFAOYSA-N 1-(4-isocyanatophenyl)pyrrole-2,5-dione Chemical compound C1=CC(N=C=O)=CC=C1N1C(=O)C=CC1=O OJQSISYVGFJJBY-UHFFFAOYSA-N 0.000 description 2
- OWDQCSBZQVISPN-UHFFFAOYSA-N 2-[(2,5-dioxopyrrolidin-1-yl)amino]-4-(2-iodoacetyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(=O)CI)C=C1NN1C(=O)CCC1=O OWDQCSBZQVISPN-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- LQILVUYCDHSGEU-UHFFFAOYSA-N 4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1CN1C(=O)C=CC1=O LQILVUYCDHSGEU-UHFFFAOYSA-N 0.000 description 2
- HBEDKBRARKFPIC-UHFFFAOYSA-N 6-(2,5-dioxopyrrol-1-yl)hexanoic acid;1-hydroxypyrrolidine-2,5-dione Chemical compound ON1C(=O)CCC1=O.OC(=O)CCCCCN1C(=O)C=CC1=O HBEDKBRARKFPIC-UHFFFAOYSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 2
- 102000049320 CD36 Human genes 0.000 description 2
- 108010045374 CD36 Antigens Proteins 0.000 description 2
- 108010065524 CD52 Antigen Proteins 0.000 description 2
- 102100027221 CD81 antigen Human genes 0.000 description 2
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 102100036369 Carbonic anhydrase 6 Human genes 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 2
- 102100032768 Complement receptor type 2 Human genes 0.000 description 2
- 108010049207 Death Domain Receptors Proteins 0.000 description 2
- 102000009058 Death Domain Receptors Human genes 0.000 description 2
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 102000050554 Eph Family Receptors Human genes 0.000 description 2
- 108091008815 Eph receptors Proteins 0.000 description 2
- 108010055196 EphA2 Receptor Proteins 0.000 description 2
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 2
- 102400001368 Epidermal growth factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 2
- 101000714525 Homo sapiens Carbonic anhydrase 6 Proteins 0.000 description 2
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 2
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 2
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101001024703 Homo sapiens Nck-associated protein 5 Proteins 0.000 description 2
- 101001099381 Homo sapiens Peroxisomal biogenesis factor 19 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102100020873 Interleukin-2 Human genes 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102100039064 Interleukin-3 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- XNSAINXGIQZQOO-UHFFFAOYSA-N L-pyroglutamyl-L-histidyl-L-proline amide Natural products NC(=O)C1CCCN1C(=O)C(NC(=O)C1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-UHFFFAOYSA-N 0.000 description 2
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 102100036946 Nck-associated protein 5 Human genes 0.000 description 2
- 108090000742 Neurotrophin 3 Proteins 0.000 description 2
- 102100029268 Neurotrophin-3 Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 102100038883 Peroxisomal biogenesis factor 19 Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 238000011579 SCID mouse model Methods 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
- 102100025131 T-cell differentiation antigen CD6 Human genes 0.000 description 2
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 2
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 239000000627 Thyrotropin-Releasing Hormone Substances 0.000 description 2
- 102400000336 Thyrotropin-releasing hormone Human genes 0.000 description 2
- 101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 description 2
- 239000002253 acid Substances 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
- 239000003098 androgen Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 238000010504 bond cleavage reaction Methods 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000005879 dioxolanyl group Chemical group 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 125000005414 dithiopyridyl group Chemical group 0.000 description 2
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- 150000003883 epothilone derivatives Chemical class 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 102000006815 folate receptor Human genes 0.000 description 2
- 108020005243 folate receptor Proteins 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 108010093470 monomethyl auristatin E Proteins 0.000 description 2
- ZNALDVNNEBOGGN-UHFFFAOYSA-N n-(2,5-dioxopyrrol-1-yl)propanamide Chemical compound CCC(=O)NN1C(=O)C=CC1=O ZNALDVNNEBOGGN-UHFFFAOYSA-N 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000006501 nitrophenyl group Chemical group 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229920000889 poly(m-phenylene isophthalamide) Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000006920 protein precipitation Effects 0.000 description 2
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000008261 resistance mechanism Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 229940034199 thyrotropin-releasing hormone Drugs 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- HTGPNFWIXOPNIF-UHFFFAOYSA-N (2,5-dioxopyrrol-1-yl) hexanoate Chemical compound CCCCCC(=O)ON1C(=O)C=CC1=O HTGPNFWIXOPNIF-UHFFFAOYSA-N 0.000 description 1
- WCMOHMXWOOBVMZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCN1C(=O)C=CC1=O WCMOHMXWOOBVMZ-UHFFFAOYSA-N 0.000 description 1
- WOWDZACBATWTAU-FEFUEGSOSA-N (2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-n-[(3r,4s,5s)-1-[(2s)-2-[(1r,2r)-3-[[(1s,2r)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)C1=CC=CC=C1 WOWDZACBATWTAU-FEFUEGSOSA-N 0.000 description 1
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical class OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical class OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QLMKIWQIZQHVHO-UHFFFAOYSA-N 3-(2,5-dioxopyrrol-1-yl)propanamide Chemical compound NC(=O)CCN1C(=O)C=CC1=O QLMKIWQIZQHVHO-UHFFFAOYSA-N 0.000 description 1
- QXZBMSIDSOZZHK-DOPDSADYSA-N 31362-50-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CNC=N1 QXZBMSIDSOZZHK-DOPDSADYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 102000005606 Activins Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 208000004881 Amebiasis Diseases 0.000 description 1
- 206010001980 Amoebiasis Diseases 0.000 description 1
- 101100377807 Arabidopsis thaliana ABCI1 gene Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102100031092 C-C motif chemokine 3 Human genes 0.000 description 1
- 101710155856 C-C motif chemokine 3 Proteins 0.000 description 1
- 108010009575 CD55 Antigens Proteins 0.000 description 1
- 102100022002 CD59 glycoprotein Human genes 0.000 description 1
- 102400000113 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229930188224 Cryptophycin Natural products 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 229940126161 DNA alkylating agent Drugs 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 102100031517 Fc receptor-like protein 1 Human genes 0.000 description 1
- 102100031511 Fc receptor-like protein 2 Human genes 0.000 description 1
- 102100031512 Fc receptor-like protein 3 Human genes 0.000 description 1
- 102100031513 Fc receptor-like protein 4 Human genes 0.000 description 1
- 102100031507 Fc receptor-like protein 5 Human genes 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100035139 Folate receptor alpha Human genes 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 206010019315 Heart transplant rejection Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 1
- 101000846913 Homo sapiens Fc receptor-like protein 1 Proteins 0.000 description 1
- 101000846911 Homo sapiens Fc receptor-like protein 2 Proteins 0.000 description 1
- 101000846910 Homo sapiens Fc receptor-like protein 3 Proteins 0.000 description 1
- 101000846909 Homo sapiens Fc receptor-like protein 4 Proteins 0.000 description 1
- 101000846908 Homo sapiens Fc receptor-like protein 5 Proteins 0.000 description 1
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 1
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 1
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 description 1
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 101000834948 Homo sapiens Tomoregulin-2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 108010041012 Integrin alpha4 Proteins 0.000 description 1
- 102000008607 Integrin beta3 Human genes 0.000 description 1
- 108010020950 Integrin beta3 Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 206010024715 Liver transplant rejection Diseases 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010051604 Lung transplant rejection Diseases 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102100039373 Membrane cofactor protein Human genes 0.000 description 1
- 108090000015 Mesothelin Proteins 0.000 description 1
- 102000003735 Mesothelin Human genes 0.000 description 1
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 102400000834 Relaxin A chain Human genes 0.000 description 1
- 101800000074 Relaxin A chain Proteins 0.000 description 1
- 102400000610 Relaxin B chain Human genes 0.000 description 1
- 101710109558 Relaxin B chain Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 1
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 1
- 102100026160 Tomoregulin-2 Human genes 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 201000011186 acute T cell leukemia Diseases 0.000 description 1
- 125000006852 aliphatic spacer Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 229940094957 androgens and estrogen Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 108010006226 cryptophycin Proteins 0.000 description 1
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 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
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 125000002704 decyl 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])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005070 decynyl 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])C([H])([H])C#C* 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Substances OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 229930188854 dolastatin Natural products 0.000 description 1
- 229940115080 doxil Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940046236 drug tradename Drugs 0.000 description 1
- 238000001425 electrospray ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 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
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 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
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 239000003168 generic drug Substances 0.000 description 1
- 201000006592 giardiasis Diseases 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- QCCOFYVWZXCXRQ-UHFFFAOYSA-N hexanoic acid;pyrrole-2,5-dione Chemical compound O=C1NC(=O)C=C1.O=C1NC(=O)C=C1.CCCCCC(O)=O QCCOFYVWZXCXRQ-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 108010021315 integrin beta7 Proteins 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical group NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 238000012434 mixed-mode chromatography Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 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
- 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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 125000000466 oxiranyl group Chemical group 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
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- VSIVTUIKYVGDCX-UHFFFAOYSA-M sodium;4-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].COC1=CC([N+]([O-])=O)=CC=C1[N+]1=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=NN1C1=CC=C([N+]([O-])=O)C=C1 VSIVTUIKYVGDCX-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 229940063683 taxotere Drugs 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
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 108010042974 transforming growth factor beta4 Proteins 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229930184737 tubulysin Natural products 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
Images
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2009/059620 WO2010126551A1 (en) | 2009-04-30 | 2009-10-06 | Potent conjugates and hydrophilic linkers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013506709A JP2013506709A (ja) | 2013-02-28 |
| JP2013506709A5 true JP2013506709A5 (enExample) | 2013-04-11 |
Family
ID=46467238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012533123A Pending JP2013506709A (ja) | 2009-10-06 | 2009-10-06 | 有効なコンジュゲートおよび親水性リンカー |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP2486023A4 (enExample) |
| JP (1) | JP2013506709A (enExample) |
| KR (1) | KR20120080611A (enExample) |
| CN (1) | CN102596922A (enExample) |
| IL (1) | IL219020A0 (enExample) |
| IN (1) | IN2012DN02780A (enExample) |
| WO (1) | WO2010126551A1 (enExample) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3014224C (en) | 2009-02-05 | 2022-05-24 | Immunogen, Inc. | Condensed benzodiazepine-indoline derivatives and processes to prepare said derivatives |
| LT2544719T (lt) | 2010-03-12 | 2019-10-25 | Debiopharm Int Sa | Cd37 surišančios molekulės, ir jų imunokonjugatai |
| EP2640727B1 (en) * | 2010-11-17 | 2015-05-13 | Genentech, Inc. | Alaninyl maytansinol antibody conjugates |
| WO2012086857A1 (ko) * | 2010-12-21 | 2012-06-28 | (주)파낙스이엠 | 광역학 진단 또는 치료를 위한 결합체 및 이의 제조방법 |
| SI2675480T1 (sl) | 2011-02-15 | 2019-05-31 | Immunogen, Inc. | Metode priprave konjugatov |
| AU2012236210B2 (en) | 2011-04-01 | 2016-02-04 | Immunogen, Inc. | CD37-binding molecules and immunoconjugates thereof |
| JP2014533954A (ja) * | 2011-11-21 | 2014-12-18 | イミュノジェン， インコーポレイテッド | Ｅｇｆｒ抗体細胞傷害性薬物複合体による、ｅｇｆｒ療法に耐性である腫瘍の治療方法 |
| US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
| CN103044677A (zh) * | 2012-12-28 | 2013-04-17 | 上海景宇生物科技有限公司 | 一种异端基遥爪聚乙二醇及其制备方法 |
| CN103083652B (zh) * | 2013-02-06 | 2016-08-10 | 中国科学院过程工程研究所 | 一种以异型双功能试剂为连接桥的脑膜炎多糖结合疫苗及其制备方法 |
| US9415118B2 (en) * | 2013-03-13 | 2016-08-16 | Novartis Ag | Antibody drug conjugates |
| US9498532B2 (en) * | 2013-03-13 | 2016-11-22 | Novartis Ag | Antibody drug conjugates |
| EP3964237B1 (en) | 2013-03-15 | 2026-02-18 | Regeneron Pharmaceuticals, Inc. | Biologically active molecules, conjugates thereof, and therapeutic uses |
| CN103254311B (zh) * | 2013-05-09 | 2015-05-13 | 齐鲁制药有限公司 | 一种制备抗体-美登素类生物碱药物偶联物的方法 |
| US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
| MX2016001541A (es) * | 2013-08-02 | 2016-08-18 | Sanofi Sa | Uso de anticuerpo inmunoconjugado anti-muc1 maitansinoide para el tratamiento de tumores solidos. |
| AU2014311361B2 (en) * | 2013-08-26 | 2018-11-29 | Regeneron Pharmaceuticals, Inc. | Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses |
| CN103483357B (zh) * | 2013-10-12 | 2015-11-18 | 齐鲁制药有限公司 | 一种抗体-美登素偶联物的中间体新晶型及其制备方法 |
| PT3057585T (pt) | 2013-10-15 | 2020-10-21 | Seagen Inc | Fármaco-ligadores peguilados para farmacocinética melhorada de conjugados de fármaco-ligando |
| CA2937561A1 (en) * | 2014-01-29 | 2015-08-06 | Shanghai Hengrui Pharmaceutical Co., Ltd. | Ligand-cytotoxic drug conjugate, preparation method thereof, and uses thereof |
| GB201402009D0 (en) * | 2014-02-06 | 2014-03-26 | Oncomatryx Biopharma S L | Antibody-drug conjugates and immunotoxins |
| EP3125943B1 (en) * | 2014-04-04 | 2026-04-22 | Merck Sharp & Dohme LLC | Phosphate based linkers for intracellular delivery of drug conjugates |
| US12174205B2 (en) | 2014-04-17 | 2024-12-24 | Northwestern University | Phosphatidylethanolamine-specific probes |
| MX2017001946A (es) * | 2014-08-12 | 2017-06-19 | Novartis Ag | Conjugados de farmacos con anticuerpos anti-cdh6. |
| MA40539A (fr) * | 2014-09-02 | 2016-03-10 | Immunogen Inc | Procédés de formulation de compositions de conjugués anticorps-médicaments |
| PT3271329T (pt) * | 2015-03-19 | 2021-10-25 | Hangzhou Dac Biotech Co Ltd | Novos ligantes hidrofílicos e conjugados ligando-fármaco dos mesmos |
| CA2978340C (en) | 2015-03-27 | 2024-05-28 | Regeneron Pharmaceuticals, Inc. | Maytansinoid derivatives, conjugates thereof, and methods of use |
| BR112017026027A2 (pt) | 2015-06-08 | 2018-08-14 | Debiopharm Int Sa | combinações de imunoconjugado anti-cd37 e anticorpo anti-cd20 |
| EP3778602B1 (en) | 2015-07-21 | 2023-07-12 | ImmunoGen, Inc. | Methods of preparing cytotoxic benzodiazepine derivatives |
| JP6890581B2 (ja) | 2015-08-28 | 2021-06-18 | デビオファーム インターナショナル， エス． アー． | Ｃｄ３７の検出のための抗体およびアッセイ |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| CN105435241A (zh) * | 2015-12-10 | 2016-03-30 | 浙江大学 | 一种iRGD-抗癌药物偶联物及其制备方法和应用 |
| MX390630B (es) | 2016-01-25 | 2025-03-21 | Regeneron Pharma | Derivados de maitansinoide, conjugados de los mismos y metodos de uso. |
| EP3433278A4 (en) | 2016-03-25 | 2019-11-06 | Seattle Genetics, Inc. | METHOD FOR THE PRODUCTION OF PEGYLATED ACTIVE LINKERS AND INTERMEDIATE PRODUCTS THEREOF |
| US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
| GB201615725D0 (en) | 2016-09-15 | 2016-11-02 | Polytherics Ltd | Novel cytotoxic agents and conjugates thereof |
| KR102520731B1 (ko) * | 2016-09-23 | 2023-04-14 | 리제너론 파아마슈티컬스, 인크. | 항-steap2 항체, 항체-약물 컨쥬게이트, 및 steap2 및 cd3에 결합하는 이중특이적 항원-결합 분자, 및 이의 용도 |
| US11278629B2 (en) | 2016-11-02 | 2022-03-22 | Debiopharm International, S.A. | Methods for improving anti-CD37 immunoconjugate therapy |
| EP3554544A4 (en) | 2016-12-16 | 2020-07-29 | Bluefin Biomedicine, Inc. | ANTI-PROTEIN 1 ANTIBODY CONTAINING AN ANTI-CUB DOMAIN (CDCP1), ANTIBODY-DRUG CONJUGATES AND THEIR METHODS OF USE |
| JP7527787B2 (ja) | 2017-03-24 | 2024-08-05 | シージェン インコーポレイテッド | グルクロニド薬物－リンカーの調製のためのプロセスおよびその中間体 |
| US11932650B2 (en) | 2017-05-11 | 2024-03-19 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
| US10646585B2 (en) | 2017-09-15 | 2020-05-12 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and ligand-drug conjugates thereof |
| US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
| SG11202002967SA (en) * | 2017-11-01 | 2020-05-28 | Arrowhead Pharmaceuticals Inc | Integrin ligands and uses thereof |
| AU2019277836A1 (en) | 2018-05-30 | 2021-01-21 | Debiopharm International, S.A. | Anti-CD37 immunoconjugate dosing regimens |
| MX2020013466A (es) * | 2018-06-26 | 2021-04-19 | Immunogen Inc | Inmunoconjugados dirigidos a adam9 y métodos para usarlos. |
| WO2020247054A1 (en) | 2019-06-05 | 2020-12-10 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
| EP4021511A4 (en) * | 2019-08-28 | 2023-10-04 | Starpharma Pty Ltd | TARGETED DENDRIMER CONJUGATES |
| WO2022182415A1 (en) | 2021-02-24 | 2022-09-01 | Massachusetts Institute Of Technology | Himastatin derivatives, and processes of preparation thereof, and uses thereof |
| WO2022216920A1 (en) | 2021-04-08 | 2022-10-13 | Arrowhead Pharmaceuticals, Inc. | Rnai agents for inhibiting expression of receptor for advanced glycation end-products, compositions thereof, and methods of use |
| CN119780422B (zh) * | 2024-11-19 | 2025-11-07 | 深圳市锦瑞生物科技股份有限公司 | 碱性磷酸酶抗体标记物及其制备方法、检测试剂和试剂盒 |
Family Cites Families (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
| US4563304A (en) | 1981-02-27 | 1986-01-07 | Pharmacia Fine Chemicals Ab | Pyridine compounds modifying proteins, polypeptides or polysaccharides |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| PT1024191E (pt) | 1991-12-02 | 2008-12-22 | Medical Res Council | Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos |
| EP0563475B1 (en) | 1992-03-25 | 2000-05-31 | Immunogen Inc | Cell binding agent conjugates of derivatives of CC-1065 |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
| GB9320575D0 (en) | 1993-10-06 | 1993-11-24 | Amp Gmbh | Coaxial connector having improved locking mechanism |
| IL111748A0 (en) | 1993-12-03 | 1995-01-24 | Zeneca Ltd | Proteins |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| US6355780B1 (en) | 1995-02-22 | 2002-03-12 | Yeda Research And Development Co. Ltd. | Antibodies to the death domain motifs of regulatory proteins |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| US6680311B1 (en) | 1996-08-30 | 2004-01-20 | Eli Lilly And Company | Cryptophycin compounds |
| FR2763066B1 (fr) | 1997-05-08 | 2001-01-05 | Agency Ind Science Techn | Nouveau compose d'ester aromatique et materiau optique non lineaire de second ordre qui en est produit |
| WO1999006587A2 (en) | 1997-08-01 | 1999-02-11 | Morphosys Ag | Novel method and phage for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex |
| US7115396B2 (en) | 1998-12-10 | 2006-10-03 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| US7303749B1 (en) | 1999-10-01 | 2007-12-04 | Immunogen Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| HK1049997B (en) | 1999-11-24 | 2007-02-23 | Immunogen, Inc. | Cytotoxic agents comprising taxanes and their therapeutic use |
| AU767394C (en) | 1999-12-29 | 2005-04-21 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
| US6956036B1 (en) | 2000-03-17 | 2005-10-18 | Alcon, Inc. | 6-hydroxy-indazole derivatives for treating glaucoma |
| US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
| US6596503B1 (en) | 2000-08-18 | 2003-07-22 | East Carolina University | Monoclonal antibody DS6, tumor-associated antigen CA6, and methods of use thereof |
| US6747021B2 (en) | 2000-10-02 | 2004-06-08 | Eli Lilly And Company | Cryptophycin compound |
| US6989450B2 (en) | 2000-10-13 | 2006-01-24 | The University Of Mississippi | Synthesis of epothilones and related analogs |
| US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
| US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
| US6560782B2 (en) | 2001-06-11 | 2003-05-13 | Playtex Products, Inc. | Antimicrobial glove and method of making same |
| US6716821B2 (en) * | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
| DE10202419A1 (de) | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
| US6534660B1 (en) | 2002-04-05 | 2003-03-18 | Immunogen, Inc. | CC-1065 analog synthesis |
| US6756397B2 (en) | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
| US6596757B1 (en) | 2002-05-14 | 2003-07-22 | Immunogen Inc. | Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use |
| EP1521769B1 (de) | 2002-07-09 | 2015-09-09 | Dömling, Alexander | Tubulysinkonjugate |
| ES2369542T3 (es) | 2002-07-31 | 2011-12-01 | Seattle Genetics, Inc. | Conjugados de auristatina y su uso para tratar cáncer, una enfermedad autoinmune o una enfermedad infecciosa. |
| EP1542723B1 (en) | 2002-08-16 | 2011-02-23 | ImmunoGen, Inc. | Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs |
| DK1578446T3 (en) | 2002-11-07 | 2015-06-29 | Immunogen Inc | ANTI-CD33 ANTIBODIES AND PROCEDURES FOR TREATING ACUTE MYELOID LEUKEMIA BY USING IT |
| EP2669377A3 (en) | 2003-04-17 | 2015-10-14 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
| US8088387B2 (en) * | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
| EP1651162B1 (en) * | 2003-05-20 | 2015-10-21 | ImmunoGen, Inc. | Improved cytotoxic agents comprising new maytansinoids |
| US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
| US7595306B2 (en) | 2003-06-09 | 2009-09-29 | Alnylam Pharmaceuticals Inc | Method of treating neurodegenerative disease |
| ES2905724T3 (es) | 2003-06-13 | 2022-04-11 | Alnylam Europe Ag | Acido ribonucleico bicatenario con elevada eficacia en un organismo |
| AU2005323437B2 (en) | 2004-04-30 | 2011-10-06 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a C5-modified pyrimidine |
| NZ551180A (en) | 2004-06-01 | 2009-10-30 | Genentech Inc | Antibody drug conjugates and methods |
| JP2008504840A (ja) | 2004-06-30 | 2008-02-21 | アルニラム ファーマスーティカルズ インコーポレイテッド | 非リン酸骨格結合を含むオリゴヌクレオチド |
| AU2005328382C1 (en) | 2004-07-21 | 2013-01-24 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
| JP4193771B2 (ja) | 2004-07-27 | 2008-12-10 | セイコーエプソン株式会社 | 階調電圧発生回路及び駆動回路 |
| EP1913011B1 (en) | 2004-08-04 | 2016-11-02 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
| AU2004224925C1 (en) | 2004-08-30 | 2011-07-21 | Biotest Ag | Immunoconjugates targeting syndecan-1 expressing cells and use thereof |
| TR201808537T4 (tr) * | 2004-09-23 | 2018-07-23 | Genentech Inc | Sistein değiştirilmiş antikorlar ve konjugatlar. |
| US20080305044A1 (en) | 2004-11-29 | 2008-12-11 | Seattle Genetics, Inc. | Engineered Antibodies and Immunoconjugates |
| KR101281501B1 (ko) | 2004-12-09 | 2013-07-15 | 얀센 바이오테크 인코포레이티드 | 항인테그린 면역 컨쥬게이트, 방법 및 용도 |
| WO2006076610A2 (en) | 2005-01-14 | 2006-07-20 | Cabot Corporation | Controlling ink migration during the formation of printable electronic features |
| US7301019B2 (en) | 2005-01-21 | 2007-11-27 | Immunogen, Inc. | Method for the preparation of maytansinoid esters |
| US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| EP1962961B1 (en) | 2005-11-29 | 2013-01-09 | The University Of Sydney | Demibodies: dimerisation-activated therapeutic agents |
| EP1996612A4 (en) | 2006-03-03 | 2010-10-20 | Univ Kingston | COMPOSITIONS FOR THE TREATMENT OF CANCER |
| PT2032606E (pt) * | 2006-05-30 | 2014-02-05 | Genentech Inc | Anticorpos e imunoconjugados e respetivas utilizações |
| CA2655379A1 (en) | 2006-06-22 | 2007-12-27 | Walter And Eliza Hall Institute Of Medical Research | Structure of the insulin receptor ectodomain |
| PE20140625A1 (es) * | 2007-07-16 | 2014-05-29 | Genentech Inc | ANTICUERPOS ANTI-CD79b E INMUNOCONJUGADOS HUMANIZADOS |
| UA108598C2 (xx) * | 2008-04-30 | 2015-05-25 | Високоефективні кон'югати та гідрофільні зшиваючі агенти (лінкери) |
-
2009
- 2009-10-06 CN CN2009801623736A patent/CN102596922A/zh active Pending
- 2009-10-06 IN IN2780DEN2012 patent/IN2012DN02780A/en unknown
- 2009-10-06 WO PCT/US2009/059620 patent/WO2010126551A1/en not_active Ceased
- 2009-10-06 EP EP09844200.7A patent/EP2486023A4/en not_active Withdrawn
- 2009-10-06 KR KR1020127010084A patent/KR20120080611A/ko not_active Withdrawn
- 2009-10-06 JP JP2012533123A patent/JP2013506709A/ja active Pending
-
2012
- 2012-04-03 IL IL219020A patent/IL219020A0/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5980989B2 (ja) | 有効なコンジュゲートおよび親水性リンカー | |
| JP2013506709A (ja) | 有効なコンジュゲートおよび親水性リンカー | |
| JP5926759B2 (ja) | 非開裂リンカーを介して連結した細胞結合物質メイタンシノイド複合体を用いて特定の細胞集団を標的とする方法、前記複合体、および前記複合体の製造法 | |
| NO20231301A1 (no) | Fremgangsmåte for målsøking av spesifikke cellepopulasjoner ved å benytte cellebindingsmiddel-maytansinoidkonjugater bundet via en ikke-kløyvbar linker, nevnte konjugater og fremstilling av nevnte konjugater. | |
| KR20070120156A (ko) | 종양에서 이종 또는 혼성 세포 집단의 제거 방법 |