SK15582003A3 - Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK15582003A3 SK15582003A3 SK1558-2003A SK15582003A SK15582003A3 SK 15582003 A3 SK15582003 A3 SK 15582003A3 SK 15582003 A SK15582003 A SK 15582003A SK 15582003 A3 SK15582003 A3 SK 15582003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- antibody
- cytotoxic
- antibody molecule
- adenocarcinoma
- maytansinoid
- Prior art date
Links
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 title claims abstract description 49
- 102100032912 CD44 antigen Human genes 0.000 title claims abstract description 45
- 231100000433 cytotoxic Toxicity 0.000 title claims abstract description 27
- 230000001472 cytotoxic effect Effects 0.000 title claims abstract description 27
- 229940127121 immunoconjugate Drugs 0.000 title claims description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 78
- 238000011282 treatment Methods 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 34
- 125000005647 linker group Chemical group 0.000 claims description 18
- 231100000167 toxic agent Toxicity 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 13
- 239000003440 toxic substance Substances 0.000 claims description 13
- 231100000331 toxic Toxicity 0.000 claims description 12
- 230000002588 toxic effect Effects 0.000 claims description 12
- 208000009956 adenocarcinoma Diseases 0.000 claims description 11
- 201000008274 breast adenocarcinoma Diseases 0.000 claims description 9
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 7
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 7
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 6
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 claims description 5
- 230000002685 pulmonary effect Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002228 disulfide group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 3
- 102000048851 human CD44 Human genes 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 108010058905 CD44v6 antigen Proteins 0.000 claims 3
- 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 claims 3
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims 3
- 208000034254 Squamous cell carcinoma of the cervix uteri Diseases 0.000 claims 3
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 claims 3
- 201000006612 cervical squamous cell carcinoma Diseases 0.000 claims 3
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims 3
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims 3
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims 3
- 201000010897 colon adenocarcinoma Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 2
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 76
- 239000000562 conjugate Substances 0.000 description 34
- 239000000427 antigen Substances 0.000 description 26
- 108091007433 antigens Proteins 0.000 description 25
- 102000036639 antigens Human genes 0.000 description 25
- 229960005558 mertansine Drugs 0.000 description 25
- 150000001413 amino acids Chemical group 0.000 description 23
- 230000027455 binding Effects 0.000 description 23
- 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 23
- 241000699670 Mus sp. Species 0.000 description 22
- 241000282414 Homo sapiens Species 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 206010041823 squamous cell carcinoma Diseases 0.000 description 11
- 241000699660 Mus musculus Species 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 9
- 238000011580 nude mouse model Methods 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 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 8
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 231100000135 cytotoxicity Toxicity 0.000 description 7
- 230000003013 cytotoxicity Effects 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 108020004707 nucleic acids Proteins 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 150000007523 nucleic acids Chemical class 0.000 description 7
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 125000004434 sulfur atom Chemical group 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 231100000682 maximum tolerated dose Toxicity 0.000 description 6
- 229960000485 methotrexate Drugs 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- 239000007987 MES buffer Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229940072221 immunoglobulins Drugs 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- QWPXBEHQFHACTK-KZVYIGENSA-N (10e,12e)-86-chloro-12,14,4-trihydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-15,16-dihydro-14h-7-aza-1(6,4)-oxazina-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-6-one Chemical compound CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-KZVYIGENSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 4
- XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 description 4
- YKRQRPFODDJQTC-CSMHCCOUSA-N Thr-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN YKRQRPFODDJQTC-CSMHCCOUSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000003636 chemical group Chemical group 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- HJVJLAOFAYPFHL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-pyridin-2-ylpropanedithioate Chemical compound C=1C=CC=NC=1C(C)C(=S)SN1C(=O)CCC1=O HJVJLAOFAYPFHL-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- LRKCBIUDWAXNEG-CSMHCCOUSA-N Leu-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRKCBIUDWAXNEG-CSMHCCOUSA-N 0.000 description 3
- 229930126263 Maytansine Natural products 0.000 description 3
- QWPXBEHQFHACTK-UHFFFAOYSA-N Maytansinol Natural products CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-UHFFFAOYSA-N 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- XQJCEKXQUJQNNK-ZLUOBGJFSA-N Ser-Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O XQJCEKXQUJQNNK-ZLUOBGJFSA-N 0.000 description 3
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 3
- ACGIVBXINJFALS-HKUYNNGSSA-N Trp-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N ACGIVBXINJFALS-HKUYNNGSSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000006023 anti-tumor response Effects 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 125000005414 dithiopyridyl group Chemical group 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000005917 in vivo anti-tumor Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 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 3
- 239000002609 medium Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- VQZYZXLBKBUOHE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)butanoate Chemical compound C=1C=CC=NC=1SSC(C)CC(=O)ON1C(=O)CCC1=O VQZYZXLBKBUOHE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AUXMWYRZQPIXCC-KNIFDHDWSA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O AUXMWYRZQPIXCC-KNIFDHDWSA-N 0.000 description 2
- -1 2-pyridyldithio Chemical group 0.000 description 2
- BUQICHWNXBIBOG-LMVFSUKVSA-N Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)N BUQICHWNXBIBOG-LMVFSUKVSA-N 0.000 description 2
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 2
- CKAJHWFHHFSCDT-WHFBIAKZSA-N Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O CKAJHWFHHFSCDT-WHFBIAKZSA-N 0.000 description 2
- GYWQGGUCMDCUJE-DLOVCJGASA-N Asp-Phe-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O GYWQGGUCMDCUJE-DLOVCJGASA-N 0.000 description 2
- VNXQRBXEQXLERQ-CIUDSAMLSA-N Asp-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N VNXQRBXEQXLERQ-CIUDSAMLSA-N 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- WVLZTXGTNGHPBO-SRVKXCTJSA-N Cys-Leu-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O WVLZTXGTNGHPBO-SRVKXCTJSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 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 2
- 108090000371 Esterases Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- SNFUTDLOCQQRQD-ZKWXMUAHSA-N Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O SNFUTDLOCQQRQD-ZKWXMUAHSA-N 0.000 description 2
- YGLCLCMAYUYZSG-AVGNSLFASA-N Glu-Lys-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 YGLCLCMAYUYZSG-AVGNSLFASA-N 0.000 description 2
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 2
- WMDZARSFSMZOQO-DRZSPHRISA-N Ile-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WMDZARSFSMZOQO-DRZSPHRISA-N 0.000 description 2
- HFKJBCPRWWGPEY-BQBZGAKWSA-N L-arginyl-L-glutamic acid Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HFKJBCPRWWGPEY-BQBZGAKWSA-N 0.000 description 2
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 2
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 2
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 2
- NRFGTHFONZYFNY-MGHWNKPDSA-N Leu-Ile-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NRFGTHFONZYFNY-MGHWNKPDSA-N 0.000 description 2
- OTXBNHIUIHNGAO-UWVGGRQHSA-N Leu-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN OTXBNHIUIHNGAO-UWVGGRQHSA-N 0.000 description 2
- KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 description 2
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 2
- 229910010199 LiAl Inorganic materials 0.000 description 2
- SWWCDAGDQHTKIE-RHYQMDGZSA-N Lys-Arg-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWWCDAGDQHTKIE-RHYQMDGZSA-N 0.000 description 2
- SQXZLVXQXWILKW-KKUMJFAQSA-N Lys-Ser-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SQXZLVXQXWILKW-KKUMJFAQSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- BPCLGWHVPVTTFM-QWRGUYRKSA-N Phe-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O BPCLGWHVPVTTFM-QWRGUYRKSA-N 0.000 description 2
- FSXRLASFHBWESK-HOTGVXAUSA-N Phe-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 FSXRLASFHBWESK-HOTGVXAUSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- ZIFYDQAFEMIZII-GUBZILKMSA-N Ser-Leu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZIFYDQAFEMIZII-GUBZILKMSA-N 0.000 description 2
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- VPZKQTYZIVOJDV-LMVFSUKVSA-N Thr-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(O)=O VPZKQTYZIVOJDV-LMVFSUKVSA-N 0.000 description 2
- BECPPKYKPSRKCP-ZDLURKLDSA-N Thr-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O BECPPKYKPSRKCP-ZDLURKLDSA-N 0.000 description 2
- WXVIGTAUZBUDPZ-DTLFHODZSA-N Thr-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 WXVIGTAUZBUDPZ-DTLFHODZSA-N 0.000 description 2
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 2
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- DZHDVYLBNKMLMB-ZFWWWQNUSA-N Trp-Lys Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCCN)C(O)=O)=CNC2=C1 DZHDVYLBNKMLMB-ZFWWWQNUSA-N 0.000 description 2
- QJBWZNTWJSZUOY-UWJYBYFXSA-N Tyr-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QJBWZNTWJSZUOY-UWJYBYFXSA-N 0.000 description 2
- YLRLHDFMMWDYTK-KKUMJFAQSA-N Tyr-Cys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLRLHDFMMWDYTK-KKUMJFAQSA-N 0.000 description 2
- YMUQBRQQCPQEQN-CXTHYWKRSA-N Tyr-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N YMUQBRQQCPQEQN-CXTHYWKRSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 108010081404 acein-2 Proteins 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 108010013835 arginine glutamate Proteins 0.000 description 2
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 2
- 108010038633 aspartylglutamate Proteins 0.000 description 2
- 108010092854 aspartyllysine Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 108010064235 lysylglycine Proteins 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000001668 nucleic acid synthesis Methods 0.000 description 2
- 238000013392 nude mouse xenograft model Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000011363 radioimmunotherapy Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 125000000101 thioether group Chemical group 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 108010044292 tryptophyltyrosine Proteins 0.000 description 2
- 108010079202 tyrosyl-alanyl-cysteine Proteins 0.000 description 2
- 108010003137 tyrosyltyrosine Proteins 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- DVOOXRTYGGLORL-VKHMYHEASA-N (2r)-2-(methylamino)-3-sulfanylpropanoic acid Chemical class CN[C@@H](CS)C(O)=O DVOOXRTYGGLORL-VKHMYHEASA-N 0.000 description 1
- RVLOMLVNNBWRSR-KNIFDHDWSA-N (2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O RVLOMLVNNBWRSR-KNIFDHDWSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- AGAYQLZJBWFZQV-UHFFFAOYSA-N 3-acetyloxolane-2,5-dione Chemical compound CC(=O)C1CC(=O)OC1=O AGAYQLZJBWFZQV-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 108700016228 AMP deaminases Proteins 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 1
- SUHLZMHFRALVSY-YUMQZZPRSA-N Ala-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)NCC(O)=O SUHLZMHFRALVSY-YUMQZZPRSA-N 0.000 description 1
- QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 1
- VKKYFICVTYKFIO-CIUDSAMLSA-N Arg-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N VKKYFICVTYKFIO-CIUDSAMLSA-N 0.000 description 1
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 1
- QNYWYYNQSXANBL-WDSOQIARSA-N Arg-Trp-His Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N QNYWYYNQSXANBL-WDSOQIARSA-N 0.000 description 1
- GXMSVVBIAMWMKO-BQBZGAKWSA-N Asn-Arg-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N GXMSVVBIAMWMKO-BQBZGAKWSA-N 0.000 description 1
- CQMQJWRCRQSBAF-BPUTZDHNSA-N Asn-Arg-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)N)N CQMQJWRCRQSBAF-BPUTZDHNSA-N 0.000 description 1
- PDECQIHABNQRHN-GUBZILKMSA-N Asp-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O PDECQIHABNQRHN-GUBZILKMSA-N 0.000 description 1
- JHFNSBBHKSZXKB-VKHMYHEASA-N Asp-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(O)=O JHFNSBBHKSZXKB-VKHMYHEASA-N 0.000 description 1
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 1
- OAMLVOVXNKILLQ-BQBZGAKWSA-N Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O OAMLVOVXNKILLQ-BQBZGAKWSA-N 0.000 description 1
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 1
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- AMRLSQGGERHDHJ-FXQIFTODSA-N Cys-Ala-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMRLSQGGERHDHJ-FXQIFTODSA-N 0.000 description 1
- NXTYATMDWQYLGJ-BQBZGAKWSA-N Cys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CS NXTYATMDWQYLGJ-BQBZGAKWSA-N 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 240000000731 Fagus sylvatica Species 0.000 description 1
- 235000010099 Fagus sylvatica Nutrition 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- FYYSIASRLDJUNP-WHFBIAKZSA-N Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FYYSIASRLDJUNP-WHFBIAKZSA-N 0.000 description 1
- RFTVTKBHDXCEEX-WDSKDSINSA-N Glu-Ser-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RFTVTKBHDXCEEX-WDSKDSINSA-N 0.000 description 1
- LLEUXCDZPQOJMY-AAEUAGOBSA-N Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(O)=O)=CNC2=C1 LLEUXCDZPQOJMY-AAEUAGOBSA-N 0.000 description 1
- BPCLDCNZBUYGOD-BPUTZDHNSA-N Glu-Trp-Glu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 BPCLDCNZBUYGOD-BPUTZDHNSA-N 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
- 108010024636 Glutathione Proteins 0.000 description 1
- KRRMJKMGWWXWDW-STQMWFEESA-N Gly-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KRRMJKMGWWXWDW-STQMWFEESA-N 0.000 description 1
- BIRKKBCSAIHDDF-WDSKDSINSA-N Gly-Glu-Cys Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(O)=O BIRKKBCSAIHDDF-WDSKDSINSA-N 0.000 description 1
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 1
- DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 description 1
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 1
- IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 description 1
- GMTXWRIDLGTVFC-IUCAKERBSA-N Gly-Lys-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMTXWRIDLGTVFC-IUCAKERBSA-N 0.000 description 1
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 1
- WNZOCXUOGVYYBJ-CDMKHQONSA-N Gly-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CN)O WNZOCXUOGVYYBJ-CDMKHQONSA-N 0.000 description 1
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 1
- OLIFSFOFKGKIRH-WUJLRWPWSA-N Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CN OLIFSFOFKGKIRH-WUJLRWPWSA-N 0.000 description 1
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 1
- GWNIGUKSRJBIHX-STQMWFEESA-N Gly-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)CN)O GWNIGUKSRJBIHX-STQMWFEESA-N 0.000 description 1
- 235000005612 Grewia tenax Nutrition 0.000 description 1
- 244000041633 Grewia tenax Species 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- AKEDPWJFQULLPE-IUCAKERBSA-N His-Glu-Gly Chemical compound N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O AKEDPWJFQULLPE-IUCAKERBSA-N 0.000 description 1
- CZVQSYNVUHAILZ-UWVGGRQHSA-N His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 CZVQSYNVUHAILZ-UWVGGRQHSA-N 0.000 description 1
- ILUVWFTXAUYOBW-CUJWVEQBSA-N His-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)N)O ILUVWFTXAUYOBW-CUJWVEQBSA-N 0.000 description 1
- HZWWOGWOBQBETJ-CUJWVEQBSA-N His-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N)O HZWWOGWOBQBETJ-CUJWVEQBSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100059521 Homo sapiens CD44 gene Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- JSZMKEYEVLDPDO-ACZMJKKPSA-N Ile-Cys Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CS)C(O)=O JSZMKEYEVLDPDO-ACZMJKKPSA-N 0.000 description 1
- KTGFOCFYOZQVRJ-ZKWXMUAHSA-N Ile-Glu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O KTGFOCFYOZQVRJ-ZKWXMUAHSA-N 0.000 description 1
- TWVKGYNQQAUNRN-ACZMJKKPSA-N Ile-Ser Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O TWVKGYNQQAUNRN-ACZMJKKPSA-N 0.000 description 1
- PXKACEXYLPBMAD-JBDRJPRFSA-N Ile-Ser-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PXKACEXYLPBMAD-JBDRJPRFSA-N 0.000 description 1
- GDFAOVXKHJXLEI-UHFFFAOYSA-N L-N-Boc-N-methylalanine Natural products CNC(C)C(O)=O GDFAOVXKHJXLEI-UHFFFAOYSA-N 0.000 description 1
- QLQHWWCSCLZUMA-KKUMJFAQSA-N Leu-Asp-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QLQHWWCSCLZUMA-KKUMJFAQSA-N 0.000 description 1
- XWOBNBRUDDUEEY-UWVGGRQHSA-N Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 XWOBNBRUDDUEEY-UWVGGRQHSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- VUBIPAHVHMZHCM-KKUMJFAQSA-N Leu-Tyr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CC=C(O)C=C1 VUBIPAHVHMZHCM-KKUMJFAQSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 1
- CIOWSLJGLSUOME-BQBZGAKWSA-N Lys-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O CIOWSLJGLSUOME-BQBZGAKWSA-N 0.000 description 1
- UGTZHPSKYRIGRJ-YUMQZZPRSA-N Lys-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O UGTZHPSKYRIGRJ-YUMQZZPRSA-N 0.000 description 1
- HGNRJCINZYHNOU-LURJTMIESA-N Lys-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(O)=O HGNRJCINZYHNOU-LURJTMIESA-N 0.000 description 1
- QCZYYEFXOBKCNQ-STQMWFEESA-N Lys-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QCZYYEFXOBKCNQ-STQMWFEESA-N 0.000 description 1
- IOQWIOPSKJOEKI-SRVKXCTJSA-N Lys-Ser-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IOQWIOPSKJOEKI-SRVKXCTJSA-N 0.000 description 1
- DLCAXBGXGOVUCD-PPCPHDFISA-N Lys-Thr-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DLCAXBGXGOVUCD-PPCPHDFISA-N 0.000 description 1
- RKIIYGUHIQJCBW-SRVKXCTJSA-N Met-His-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RKIIYGUHIQJCBW-SRVKXCTJSA-N 0.000 description 1
- 102100037510 Metallothionein-1E Human genes 0.000 description 1
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 241000187681 Nocardia sp. Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- MSHZERMPZKCODG-ACRUOGEOSA-N Phe-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MSHZERMPZKCODG-ACRUOGEOSA-N 0.000 description 1
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 1
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- RZEQTVHJZCIUBT-WDSKDSINSA-N Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RZEQTVHJZCIUBT-WDSKDSINSA-N 0.000 description 1
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 1
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 1
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 1
- KCFKKAQKRZBWJB-ZLUOBGJFSA-N Ser-Cys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O KCFKKAQKRZBWJB-ZLUOBGJFSA-N 0.000 description 1
- KNCJWSPMTFFJII-ZLUOBGJFSA-N Ser-Cys-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O KNCJWSPMTFFJII-ZLUOBGJFSA-N 0.000 description 1
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 1
- YZMPDHTZJJCGEI-BQBZGAKWSA-N Ser-His Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 YZMPDHTZJJCGEI-BQBZGAKWSA-N 0.000 description 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 1
- JWOBLHJRDADHLN-KKUMJFAQSA-N Ser-Leu-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JWOBLHJRDADHLN-KKUMJFAQSA-N 0.000 description 1
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 1
- OZPDGESCTGGNAD-CIUDSAMLSA-N Ser-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CO OZPDGESCTGGNAD-CIUDSAMLSA-N 0.000 description 1
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 1
- LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 1
- PCJLFYBAQZQOFE-KATARQTJSA-N Ser-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N)O PCJLFYBAQZQOFE-KATARQTJSA-N 0.000 description 1
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 1
- LZLREEUGSYITMX-JQWIXIFHSA-N Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)N)C(O)=O)=CNC2=C1 LZLREEUGSYITMX-JQWIXIFHSA-N 0.000 description 1
- GSCVDSBEYVGMJQ-SRVKXCTJSA-N Ser-Tyr-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CO)N)O GSCVDSBEYVGMJQ-SRVKXCTJSA-N 0.000 description 1
- OQSQCUWQOIHECT-YJRXYDGGSA-N Ser-Tyr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OQSQCUWQOIHECT-YJRXYDGGSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- IGROJMCBGRFRGI-YTLHQDLWSA-N Thr-Ala-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O IGROJMCBGRFRGI-YTLHQDLWSA-N 0.000 description 1
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 1
- CUTPSEKWUPZFLV-WISUUJSJSA-N Thr-Cys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(O)=O CUTPSEKWUPZFLV-WISUUJSJSA-N 0.000 description 1
- UDQBCBUXAQIZAK-GLLZPBPUSA-N Thr-Glu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UDQBCBUXAQIZAK-GLLZPBPUSA-N 0.000 description 1
- IQHUITKNHOKGFC-MIMYLULJSA-N Thr-Phe Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IQHUITKNHOKGFC-MIMYLULJSA-N 0.000 description 1
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 1
- WCRFXRIWBFRZBR-GGVZMXCHSA-N Thr-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WCRFXRIWBFRZBR-GGVZMXCHSA-N 0.000 description 1
- BEZTUFWTPVOROW-KJEVXHAQSA-N Thr-Tyr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O BEZTUFWTPVOROW-KJEVXHAQSA-N 0.000 description 1
- HQJOVVWAPQPYDS-ZFWWWQNUSA-N Trp-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQJOVVWAPQPYDS-ZFWWWQNUSA-N 0.000 description 1
- TYYLDKGBCJGJGW-WMZOPIPTSA-N Trp-Tyr Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 TYYLDKGBCJGJGW-WMZOPIPTSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- GZUIDWDVMWZSMI-KKUMJFAQSA-N Tyr-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GZUIDWDVMWZSMI-KKUMJFAQSA-N 0.000 description 1
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 1
- CGWAPUBOXJWXMS-HOTGVXAUSA-N Tyr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 CGWAPUBOXJWXMS-HOTGVXAUSA-N 0.000 description 1
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 1
- MFEVVAXTBZELLL-GGVZMXCHSA-N Tyr-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MFEVVAXTBZELLL-GGVZMXCHSA-N 0.000 description 1
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 1
- JAQGKXUEKGKTKX-HOTGVXAUSA-N Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 JAQGKXUEKGKTKX-HOTGVXAUSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 102220589754 YjeF N-terminal domain-containing protein 3_G25F_mutation Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- OPQNCARIZFLNLF-UHFFFAOYSA-N ansamitocin P-3 Natural products CN1C(=O)CC(OC(=O)C(C)C)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 OPQNCARIZFLNLF-UHFFFAOYSA-N 0.000 description 1
- OPQNCARIZFLNLF-JBHFWYGFSA-N ansamitocin P3 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(C)C)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 OPQNCARIZFLNLF-JBHFWYGFSA-N 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 description 1
- 150000001504 aryl thiols Chemical class 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 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
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 1
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010027338 isoleucylcysteine Proteins 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 1
- 108010091871 leucylmethionine Proteins 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000005960 long-lasting response Effects 0.000 description 1
- 230000004904 long-term response Effects 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 108010038320 lysylphenylalanine Proteins 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 125000005413 thiopyridyl group Chemical group 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010029384 tryptophyl-histidine Proteins 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01112227A EP1258255A1 (en) | 2001-05-18 | 2001-05-18 | Conjugates of an antibody to CD44 and a maytansinoid |
| PCT/EP2002/005413 WO2002094325A2 (en) | 2001-05-18 | 2002-05-16 | Cytotoxic cd44 antibody immunoconjugates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK15582003A3 true SK15582003A3 (sk) | 2004-04-06 |
Family
ID=8177473
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1558-2003A SK15582003A3 (sk) | 2001-05-18 | 2002-05-16 | Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie |
Country Status (24)
| Country | Link |
|---|---|
| EP (2) | EP1258255A1 (et) |
| JP (1) | JP2004529963A (et) |
| KR (1) | KR20030097883A (et) |
| CN (1) | CN1509187A (et) |
| AR (1) | AR035977A1 (et) |
| BG (1) | BG108366A (et) |
| BR (1) | BR0209862A (et) |
| CA (1) | CA2443438A1 (et) |
| CO (1) | CO5550468A2 (et) |
| CZ (1) | CZ20033477A3 (et) |
| EA (1) | EA200301159A1 (et) |
| EE (1) | EE200300568A (et) |
| HR (1) | HRP20030932A2 (et) |
| HU (1) | HUP0400046A3 (et) |
| IL (1) | IL157965A0 (et) |
| MX (1) | MXPA03010432A (et) |
| NO (1) | NO20035108D0 (et) |
| NZ (1) | NZ530167A (et) |
| PE (1) | PE20021097A1 (et) |
| PL (1) | PL365480A1 (et) |
| SK (1) | SK15582003A3 (et) |
| WO (1) | WO2002094325A2 (et) |
| YU (1) | YU91503A (et) |
| ZA (1) | ZA200307364B (et) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8071072B2 (en) * | 1999-10-08 | 2011-12-06 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US6441163B1 (en) * | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| EP1417974A1 (en) * | 2002-11-08 | 2004-05-12 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and radiotherapy |
| US7384744B2 (en) | 2002-11-29 | 2008-06-10 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | Expression vector, methods for the production of heterologous gene products and for the selection of recombinant cells producing high levels of such products |
| DE10256083A1 (de) * | 2002-11-29 | 2004-08-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Expressionsvektor, Verfahren zur Herstellung von heterologen Genprodukten und Selektionsverfahren für hochproduzierende rekombinante Zellen |
| US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
| ES2559670T3 (es) * | 2003-05-20 | 2016-02-15 | Immunogen, Inc. | Agentes citotóxicos mejorados que comprenden nuevos maitansinoides |
| CN103145844B (zh) * | 2003-07-21 | 2016-08-03 | 伊缪诺金公司 | Ca6抗原特异性细胞毒性偶联物及其应用方法 |
| CA2556027C (en) | 2004-02-12 | 2015-11-24 | Morphotek, Inc. | Monoclonal antibodies that specifically block biological activity of a tumor antigen |
| AU2005314392B2 (en) | 2004-12-09 | 2011-04-14 | Centocor, Inc. | Anti-integrin immunoconjugates, methods and uses |
| AU2006213662B2 (en) * | 2005-02-11 | 2010-08-05 | Immunogen, Inc. | Process for preparing stable drug conjugates |
| AU2006223301B2 (en) | 2005-03-10 | 2010-11-04 | Eisai, Inc. | Anti-mesothelin antibodies |
| CN101374545B (zh) * | 2005-04-15 | 2012-03-28 | 免疫基因公司 | 消除肿瘤中的异质或混合细胞群体 |
| JP2009521206A (ja) | 2005-04-22 | 2009-06-04 | モルフォテック、インク． | 免疫エフェクター活性を有する葉酸受容体アルファ陽性細胞に内部移行する抗体 |
| EP2399609B1 (en) | 2005-08-24 | 2015-03-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
| EP1806365A1 (en) * | 2006-01-05 | 2007-07-11 | Boehringer Ingelheim International GmbH | Antibody molecules specific for fibroblast activation protein and immunoconjugates containing them |
| AR059900A1 (es) * | 2006-03-17 | 2008-05-07 | Genentech Inc | Anticuerpos anti-tat226 e inmunoconjugados |
| HUE043645T2 (hu) | 2009-06-03 | 2019-08-28 | Immunogen Inc | Konjugációs módszerek |
| TW201117814A (en) * | 2009-10-02 | 2011-06-01 | Sanofi Aventis | New maytansinoids and the use of said maytansinoids to prepare conjugates with an antibody |
| PT2691155T (pt) | 2011-03-29 | 2019-02-19 | Immunogen Inc | Preparação de conjugados de anticorpo de maitansinoide por processo de uma etapa |
| CN102337298B (zh) * | 2011-08-19 | 2013-11-06 | 黄开红 | 一种输送siRNA的免疫纳米载体及其制备方法和应用 |
| CA2886993A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates |
| GB201220891D0 (en) | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating breast cancers |
| GB201220889D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating metastasizing cancers |
| GB201220901D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating pancreatic cancer |
| GB201220899D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived pegylated peptides |
| JP6608823B2 (ja) | 2013-08-26 | 2019-11-20 | レゲネロン ファーマシューティカルス，インコーポレーテッド | マクロライドジアステレオマーを含む医薬組成物、その合成方法、及び治療上の使用 |
| GB201421647D0 (en) | 2014-12-05 | 2015-01-21 | Amcure Gmbh And Ruprecht-Karls-Universitat And Karlsruher Institut F�R Technologie | CD44v6-derived cyclic peptides for treating cancers and angiogenesis related diseases |
| WO2016150521A1 (en) * | 2015-03-26 | 2016-09-29 | Fundación Imdea Nanociencia | Functionalised magnetic nanoparticle |
| JP2021519608A (ja) * | 2018-02-22 | 2021-08-12 | マルティチュード・インコーポレーテッド | 治療抗体およびその使用 |
| CN114057874B (zh) * | 2020-07-31 | 2023-05-05 | 北京市神经外科研究所 | 抗cd44的单链抗体及其在制备治疗肿瘤的药物中的用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2026147C (en) * | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5208020A (en) * | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| UY24389A1 (es) * | 1995-12-06 | 2001-10-25 | Karlsruhe Forschzent | Composición farmacéutica para el tratamiento de carcinoma de epitelio plano |
| DE19648209A1 (de) * | 1996-11-21 | 1998-05-28 | Boehringer Ingelheim Int | Verfahren zur Tumorzelldepletion CD34-positiver Zellen |
| DE19708713C2 (de) * | 1997-03-04 | 2002-11-28 | Boehringer Ingelheim Int | Verwendung von anti-CD44 Antikörpern enthaltenden Präparationen zur Behandlung bestimmter Tumore und zur Unterdrückung von Immunreaktionen |
| NZ515975A (en) * | 1999-06-25 | 2004-01-30 | Genentech Inc | Anti-ErbB antibody-maytansinoid conjugates useful in the treatment of tumors characterised by the overexpression of an ErbB receptor |
| EP1229934B1 (en) * | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
-
2001
- 2001-05-18 EP EP01112227A patent/EP1258255A1/en not_active Withdrawn
-
2002
- 2002-05-16 PL PL02365480A patent/PL365480A1/xx not_active Application Discontinuation
- 2002-05-16 BR BR0209862-8A patent/BR0209862A/pt not_active IP Right Cessation
- 2002-05-16 EP EP02753054A patent/EP1395290A2/en not_active Withdrawn
- 2002-05-16 MX MXPA03010432A patent/MXPA03010432A/es not_active Application Discontinuation
- 2002-05-16 YU YU91503A patent/YU91503A/sh unknown
- 2002-05-16 HU HU0400046A patent/HUP0400046A3/hu unknown
- 2002-05-16 CA CA002443438A patent/CA2443438A1/en not_active Abandoned
- 2002-05-16 SK SK1558-2003A patent/SK15582003A3/sk not_active Application Discontinuation
- 2002-05-16 JP JP2002591041A patent/JP2004529963A/ja active Pending
- 2002-05-16 NZ NZ530167A patent/NZ530167A/en unknown
- 2002-05-16 EA EA200301159A patent/EA200301159A1/ru unknown
- 2002-05-16 CZ CZ20033477A patent/CZ20033477A3/cs unknown
- 2002-05-16 CN CNA028101634A patent/CN1509187A/zh active Pending
- 2002-05-16 KR KR10-2003-7015037A patent/KR20030097883A/ko not_active Application Discontinuation
- 2002-05-16 EE EEP200300568A patent/EE200300568A/et unknown
- 2002-05-16 WO PCT/EP2002/005413 patent/WO2002094325A2/en not_active Application Discontinuation
- 2002-05-16 IL IL15796502A patent/IL157965A0/xx unknown
- 2002-05-17 AR ARP020101829A patent/AR035977A1/es not_active Application Discontinuation
- 2002-05-17 PE PE2002000420A patent/PE20021097A1/es not_active Application Discontinuation
-
2003
- 2003-09-22 ZA ZA200307364A patent/ZA200307364B/en unknown
- 2003-11-14 HR HR20030932A patent/HRP20030932A2/xx not_active Application Discontinuation
- 2003-11-17 BG BG108366A patent/BG108366A/bg unknown
- 2003-11-17 NO NO20035108A patent/NO20035108D0/no not_active Application Discontinuation
- 2003-11-18 CO CO03101695A patent/CO5550468A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| YU91503A (sh) | 2006-05-25 |
| EE200300568A (et) | 2004-04-15 |
| BR0209862A (pt) | 2004-06-08 |
| BG108366A (bg) | 2004-09-30 |
| ZA200307364B (en) | 2004-04-20 |
| PE20021097A1 (es) | 2003-02-13 |
| NO20035108L (no) | 2003-11-17 |
| PL365480A1 (en) | 2005-01-10 |
| KR20030097883A (ko) | 2003-12-31 |
| WO2002094325A2 (en) | 2002-11-28 |
| CA2443438A1 (en) | 2002-11-28 |
| MXPA03010432A (es) | 2004-04-02 |
| CN1509187A (zh) | 2004-06-30 |
| HUP0400046A3 (en) | 2006-02-28 |
| AR035977A1 (es) | 2004-07-28 |
| IL157965A0 (en) | 2004-03-28 |
| CZ20033477A3 (en) | 2004-05-12 |
| JP2004529963A (ja) | 2004-09-30 |
| CO5550468A2 (es) | 2005-08-31 |
| EA200301159A1 (ru) | 2004-06-24 |
| HRP20030932A2 (en) | 2004-04-30 |
| NO20035108D0 (no) | 2003-11-17 |
| EP1395290A2 (en) | 2004-03-10 |
| NZ530167A (en) | 2005-10-28 |
| WO2002094325A3 (en) | 2003-04-17 |
| EP1258255A1 (en) | 2002-11-20 |
| HUP0400046A2 (hu) | 2004-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK15582003A3 (sk) | Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie | |
| US20040126379A1 (en) | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and chemotherapeutic agents | |
| US20030103985A1 (en) | Cytotoxic CD44 antibody immunoconjugates | |
| TW200422050A (en) | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and chemotherapeutic agents | |
| JP6039751B2 (ja) | フォレート受容体１抗体及びそのイムノコンジュゲート及び使用 | |
| JP5932672B2 (ja) | Ｃｄ３７結合分子及びそのイムノコンジュゲート | |
| AU2018354189A1 (en) | Compositions and methods for the depletion of CD117+ cells | |
| US20210379195A1 (en) | Methods for allogeneic hematopoietic stem cell transplantation | |
| US20210371524A1 (en) | Anti-cd45 antibodies and conjugates thereof | |
| CN115151564A (zh) | 抗pd-l1抗体和抗体-药物缀合物 | |
| US20220062339A1 (en) | Use of an anti-cd45 antibody drug conjugate (adc) in cell therapy | |
| US20220267441A1 (en) | Anti-cd45 antibodies and conjugates thereof | |
| US20040120949A1 (en) | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and radiotherapy | |
| WO2020219964A1 (en) | Conditioning methods for gene therapy | |
| US20230390412A1 (en) | Compositions and methods for allogeneic transplantation | |
| US20220273811A1 (en) | Methods and compositions for treating autoimmune diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC9A | Refused patent application |