HRP970566A2 - Conjugates useful in the treatment of prostate canser - Google Patents

Conjugates useful in the treatment of prostate canser

Info

Publication number: HRP970566A2
Authority: HR; Croatia
Prior art keywords: seq; image; oligopeptide; alkyl; hipxaasertirgln
Prior art date: 1996-10-30

Application number

HR9718160.6A

Other languages

English (en)

Croatian (hr)

Inventor

Jones Deborah Defeo

Original Assignee

Jones Deborah Defeo

Priority date (The priority date 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 date listed.)

1996-10-30

Filing date

1997-10-24

Publication date

1998-08-31

1996-12-18 Priority claimed from GBGB9626309.0A external-priority patent/GB9626309D0/en

1997-08-28 Priority claimed from GBGB9718160.6A external-priority patent/GB9718160D0/en

1997-10-24 Application filed by Jones Deborah Defeo filed Critical Jones Deborah Defeo

1998-08-31 Publication of HRP970566A2 publication Critical patent/HRP970566A2/hr

Links

210000002307 prostate Anatomy 0.000 title description 5
108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 103
108010038807 Oligopeptides Proteins 0.000 claims description 95
102000015636 Oligopeptides Human genes 0.000 claims description 95
229940127089 cytotoxic agent Drugs 0.000 claims description 68
239000002254 cytotoxic agent Substances 0.000 claims description 68
-1 cyclic amino acid Chemical class 0.000 claims description 65
231100000599 cytotoxic agent Toxicity 0.000 claims description 63
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 claims description 54
229940024606 amino acid Drugs 0.000 claims description 51
235000001014 amino acid Nutrition 0.000 claims description 51
229910052739 hydrogen Inorganic materials 0.000 claims description 33
239000001257 hydrogen Substances 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 32
229960004679 doxorubicin Drugs 0.000 claims description 29
150000001413 amino acids Chemical class 0.000 claims description 28
125000003118 aryl group Chemical group 0.000 claims description 28
150000001875 compounds Chemical class 0.000 claims description 28
239000000203 mixture Substances 0.000 claims description 28
NFDYGNFETJVMSE-BQBZGAKWSA-N Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CO NFDYGNFETJVMSE-BQBZGAKWSA-N 0.000 claims description 26
238000000034 method Methods 0.000 claims description 23
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 claims description 20
150000002431 hydrogen Chemical class 0.000 claims description 19
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 claims description 16
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 16
230000003287 optical effect Effects 0.000 claims description 15
229960003048 vinblastine Drugs 0.000 claims description 15
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
206010060862 Prostate cancer Diseases 0.000 claims description 14
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
229940079593 drug Drugs 0.000 claims description 11
230000002255 enzymatic effect Effects 0.000 claims description 11
239000000126 substance Substances 0.000 claims description 11
230000001472 cytotoxic effect Effects 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 9
BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 claims description 8
ODKSFYDXXFIFQN-UHFFFAOYSA-N Arginine Chemical compound OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 7
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 7
208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 claims description 6
QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 claims description 6
QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
231100000433 cytotoxic Toxicity 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 6
WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 claims description 5
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 5
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 5
SSJMZMUVNKEENT-IMJSIDKUSA-N Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CO SSJMZMUVNKEENT-IMJSIDKUSA-N 0.000 claims description 5
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 5
FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 5
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
229940122803 Vinca alkaloid Drugs 0.000 claims description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
229960002591 hydroxyproline Drugs 0.000 claims description 4
229960000485 methotrexate Drugs 0.000 claims description 4
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 claims description 3
229940045799 anthracyclines and related substance Drugs 0.000 claims description 3
239000011230 binding agent Substances 0.000 claims description 3
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class 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 claims description 3
229960004397 cyclophosphamide Drugs 0.000 claims description 3
229960001842 estramustine Drugs 0.000 claims description 3
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 3
229960001924 melphalan Drugs 0.000 claims description 3
229960001428 mercaptopurine Drugs 0.000 claims description 3
YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 2
TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 claims description 2
108010006654 Bleomycin Proteins 0.000 claims description 2
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 claims description 2
LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 claims description 2
229930192392 Mitomycin Natural products 0.000 claims description 2
HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 claims description 2
229940123237 Taxane Drugs 0.000 claims description 2
229960003896 aminopterin Drugs 0.000 claims description 2
XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 claims description 2
229930188550 carminomycin Natural products 0.000 claims description 2
XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 claims description 2
229950001725 carubicin Drugs 0.000 claims description 2
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
229960004316 cisplatin Drugs 0.000 claims description 2
YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 claims description 2
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 2
229960005420 etoposide Drugs 0.000 claims description 2
LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 claims description 2
229960000752 etoposide phosphate Drugs 0.000 claims description 2
229960002949 fluorouracil Drugs 0.000 claims description 2
HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 claims description 2
229960004857 mitomycin Drugs 0.000 claims description 2
239000002777 nucleoside Substances 0.000 claims description 2
125000003835 nucleoside group Chemical group 0.000 claims description 2
229960001237 podophyllotoxin Drugs 0.000 claims description 2
YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 claims description 2
229950004406 porfiromycin Drugs 0.000 claims description 2
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
229960004528 vincristine Drugs 0.000 claims description 2
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 claims description 2
UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims description 2
229960004355 vindesine Drugs 0.000 claims description 2
102000007066 Prostate-Specific Antigen Human genes 0.000 claims 10
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 claims 1
201000009030 Carcinoma Diseases 0.000 claims 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims 1
229930012538 Paclitaxel Natural products 0.000 claims 1
235000004279 alanine Nutrition 0.000 claims 1
229940125904 compound 1 Drugs 0.000 claims 1
229960000975 daunorubicin Drugs 0.000 claims 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 1
229960000310 isoleucine Drugs 0.000 claims 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims 1
FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 claims 1
229960001592 paclitaxel Drugs 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
102100038358 Prostate-specific antigen Human genes 0.000 description 93
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
239000012071 phase Substances 0.000 description 27
108090000765 processed proteins & peptides Proteins 0.000 description 26
238000004128 high performance liquid chromatography Methods 0.000 description 19
210000002966 serum Anatomy 0.000 description 19
239000000047 product Substances 0.000 description 17
238000003776 cleavage reaction Methods 0.000 description 15
230000007017 scission Effects 0.000 description 15
229910001868 water Inorganic materials 0.000 description 15
239000000872 buffer Substances 0.000 description 14
210000004027 cell Anatomy 0.000 description 14
125000006239 protecting group Chemical group 0.000 description 14
239000011347 resin Substances 0.000 description 14
229920005989 resin Polymers 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
241001465754 Metazoa Species 0.000 description 13
125000005647 linker group Chemical group 0.000 description 13
239000000243 solution Substances 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 10
238000012360 testing method Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
230000006337 proteolytic cleavage Effects 0.000 description 8
210000001519 tissue Anatomy 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
125000000753 cycloalkyl group Chemical group 0.000 description 7
235000018102 proteins Nutrition 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
125000003275 alpha amino acid group Chemical group 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
230000014759 maintenance of location Effects 0.000 description 6
229920001223 polyethylene glycol Polymers 0.000 description 6
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
238000011156 evaluation Methods 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
238000011081 inoculation Methods 0.000 description 5
238000010647 peptide synthesis reaction Methods 0.000 description 5
102000004196 processed proteins & peptides Human genes 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
125000003107 substituted aryl group Chemical group 0.000 description 5
150000001420 substituted heterocyclic compounds Chemical class 0.000 description 5
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
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
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
125000000539 amino acid group Chemical group 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
230000001093 anti-cancer Effects 0.000 description 4
230000000903 blocking effect Effects 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
NDMPLJNOPCLANR-PETVRERISA-N deacetylvinblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 NDMPLJNOPCLANR-PETVRERISA-N 0.000 description 4
230000029087 digestion Effects 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
150000002391 heterocyclic compounds Chemical class 0.000 description 4
238000007912 intraperitoneal administration Methods 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
239000011630 iodine Substances 0.000 description 4
125000001151 peptidyl group Chemical group 0.000 description 4
230000002797 proteolythic effect Effects 0.000 description 4
238000004007 reversed phase HPLC Methods 0.000 description 4
239000008223 sterile water Substances 0.000 description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
101100392772 Caenorhabditis elegans gln-2 gene Proteins 0.000 description 3
MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
125000003435 aroyl group Chemical group 0.000 description 3
125000003710 aryl alkyl group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000007906 compression Methods 0.000 description 3
230000006835 compression Effects 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
201000010099 disease Diseases 0.000 description 3
229960002918 doxorubicin hydrochloride Drugs 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
231100001160 nonlethal Toxicity 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
239000008188 pellet Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
238000002953 preparative HPLC Methods 0.000 description 3
230000003248 secreting effect Effects 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
239000003643 water by type Substances 0.000 description 3
DMBKPDOAQVGTST-GFCCVEGCSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylmethoxypropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)COCC1=CC=CC=C1 DMBKPDOAQVGTST-GFCCVEGCSA-N 0.000 description 2
YPVWZYYJGOFZOB-ZETCQYMHSA-N (2s)-2-amino-6-(1h-imidazol-2-ylamino)hexanoic acid Chemical group OC(=O)[C@@H](N)CCCCNC1=NC=CN1 YPVWZYYJGOFZOB-ZETCQYMHSA-N 0.000 description 2
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 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 2
102100033312 Alpha-2-macroglobulin Human genes 0.000 description 2
102000004400 Aminopeptidases Human genes 0.000 description 2
108090000915 Aminopeptidases Proteins 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
102000016359 Fibronectins Human genes 0.000 description 2
108010067306 Fibronectins Proteins 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
102000004374 Insulin-like growth factor binding protein 3 Human genes 0.000 description 2
108090000965 Insulin-like growth factor binding protein 3 Proteins 0.000 description 2
102000000589 Interleukin-1 Human genes 0.000 description 2
108010002352 Interleukin-1 Proteins 0.000 description 2
102000000588 Interleukin-2 Human genes 0.000 description 2
108010002350 Interleukin-2 Proteins 0.000 description 2
102000004889 Interleukin-6 Human genes 0.000 description 2
108090001005 Interleukin-6 Proteins 0.000 description 2
206010027476 Metastases Diseases 0.000 description 2
102000035195 Peptidases Human genes 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 2
102100037550 Semenogelin-1 Human genes 0.000 description 2
101710089345 Semenogelin-1 Proteins 0.000 description 2
102100037547 Semenogelin-2 Human genes 0.000 description 2
101710089335 Semenogelin-2 Proteins 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
125000002252 acyl group Polymers 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
108010091628 alpha 1-Antichymotrypsin Proteins 0.000 description 2
QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
125000001589 carboacyl group Chemical group 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
210000000172 cytosol Anatomy 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
230000007515 enzymatic degradation Effects 0.000 description 2
239000012634 fragment Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
125000002636 imidazolinyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
229940079322 interferon Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
230000036210 malignancy Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
235000013930 proline Nutrition 0.000 description 2
210000005267 prostate cell Anatomy 0.000 description 2
230000017854 proteolysis Effects 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
NHTGHBARYWONDQ-UHFFFAOYSA-N (+-)-α-methyl-tyrosine Chemical compound OC(=O)C(N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-UHFFFAOYSA-N 0.000 description 1
WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 description 1
AMLAISDQMDUUIU-GFCCVEGCSA-N (2r)-2,6-diamino-2-(4,6-dimethylpyrimidin-2-yl)hexanoic acid Chemical compound CC1=CC(C)=NC([C@](N)(CCCCN)C(O)=O)=N1 AMLAISDQMDUUIU-GFCCVEGCSA-N 0.000 description 1
OMGHIGVFLOPEHJ-BYPYZUCNSA-N (2s)-2,5-dihydro-1h-pyrrole-2-carboxylic acid Chemical compound OC(=O)[C@H]1NCC=C1 OMGHIGVFLOPEHJ-BYPYZUCNSA-N 0.000 description 1
REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 1
WTKYBFQVZPCGAO-LURJTMIESA-N (2s)-2-(pyridin-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CN=C1 WTKYBFQVZPCGAO-LURJTMIESA-N 0.000 description 1
MCEHFIXEKNKSRW-LBPRGKRZSA-N (2s)-2-[[3,5-dichloro-4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=C(Cl)C=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1Cl MCEHFIXEKNKSRW-LBPRGKRZSA-N 0.000 description 1
HESLJQBDDBJJQQ-JTQLQIEISA-N (2s)-2-amino-3-(4-dimethoxyphosphoryloxyphenyl)propanoic acid Chemical compound COP(=O)(OC)OC1=CC=C(C[C@H](N)C(O)=O)C=C1 HESLJQBDDBJJQQ-JTQLQIEISA-N 0.000 description 1
GNVNKFUEUXUWDV-VIFPVBQESA-N (2s)-2-amino-3-[4-(aminomethyl)phenyl]propanoic acid Chemical compound NCC1=CC=C(C[C@H](N)C(O)=O)C=C1 GNVNKFUEUXUWDV-VIFPVBQESA-N 0.000 description 1
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
RPGPPCHMKDWLRT-UHFFFAOYSA-N 2-amino-3-methoxypropanenitrile Chemical compound COCC(N)C#N RPGPPCHMKDWLRT-UHFFFAOYSA-N 0.000 description 1
WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
HWNGLKPRXKKTPK-UHFFFAOYSA-N 3,4-dihydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CNC(C(O)=O)C1O HWNGLKPRXKKTPK-UHFFFAOYSA-N 0.000 description 1
VIIAUOZUUGXERI-ZETCQYMHSA-N 3-fluoro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(F)=C1 VIIAUOZUUGXERI-ZETCQYMHSA-N 0.000 description 1
UQTZMGFTRHFAAM-ZETCQYMHSA-N 3-iodo-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(I)=C1 UQTZMGFTRHFAAM-ZETCQYMHSA-N 0.000 description 1
MQHLULPKDLJASZ-QMMMGPOBSA-N 3-methyl-L-tyrosine zwitterion Chemical compound CC1=CC(C[C@H](N)C(O)=O)=CC=C1O MQHLULPKDLJASZ-QMMMGPOBSA-N 0.000 description 1
KWZYQHQNOWRQRG-UHFFFAOYSA-N 3beta-hydroxytremetone Natural products C1=C(C(C)=O)C=C2C(O)C(C(=C)C)OC2=C1 KWZYQHQNOWRQRG-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
AKMNXFPRFUKZES-UHFFFAOYSA-N 5-(9h-fluoren-1-ylmethoxy)-5-oxopentanoic acid Chemical compound C1C2=CC=CC=C2C2=C1C(COC(=O)CCCC(=O)O)=CC=C2 AKMNXFPRFUKZES-UHFFFAOYSA-N 0.000 description 1
108010066676 Abrin Proteins 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
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 1
102100023995 Beta-nerve growth factor Human genes 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
238000009010 Bradford assay Methods 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
108090000317 Chymotrypsin Proteins 0.000 description 1
QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
102000016607 Diphtheria Toxin Human genes 0.000 description 1
108010053187 Diphtheria Toxin Proteins 0.000 description 1
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 1
238000002965 ELISA Methods 0.000 description 1
102000010911 Enzyme Precursors Human genes 0.000 description 1
108010062466 Enzyme Precursors Proteins 0.000 description 1
241000283086 Equidae Species 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
101100295741 Gallus gallus COR4 gene Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
DXJZITDUDUPINW-WHFBIAKZSA-N Gln-Asn Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O DXJZITDUDUPINW-WHFBIAKZSA-N 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
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
108090000288 Glycoproteins Proteins 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
241000282412 Homo Species 0.000 description 1
102000008100 Human Serum Albumin Human genes 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
LOOZZTFGSTZNRX-VIFPVBQESA-N L-Homotyrosine Chemical compound OC(=O)[C@@H](N)CCC1=CC=C(O)C=C1 LOOZZTFGSTZNRX-VIFPVBQESA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical group [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-PJXZDTQASA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
102000008072 Lymphokines Human genes 0.000 description 1
108010074338 Lymphokines Proteins 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
241000699666 Mus <mouse, genus> Species 0.000 description 1
108010025020 Nerve Growth Factor Proteins 0.000 description 1
GEYBMYRBIABFTA-VIFPVBQESA-N O-methyl-L-tyrosine Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1 GEYBMYRBIABFTA-VIFPVBQESA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241000009328 Perro Species 0.000 description 1
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
108010039491 Ricin Proteins 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 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
241000282887 Suidae Species 0.000 description 1
102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
KWZYQHQNOWRQRG-OLZOCXBDSA-N Toxol Chemical compound C1=C(C(C)=O)C=C2[C@@H](O)[C@H](C(=C)C)OC2=C1 KWZYQHQNOWRQRG-OLZOCXBDSA-N 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
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
241000863480 Vinca Species 0.000 description 1
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-KSNABSRWSA-N 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000003797 alkaloid derivatives Chemical group 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 1
101150039027 ampH gene Proteins 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
239000003817 anthracycline antibiotic agent Substances 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940045696 antineoplastic drug podophyllotoxin derivative Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
150000008209 arabinosides Chemical class 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
108010038633 aspartylglutamate Proteins 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000004619 benzopyranyl group Chemical group O1C(C=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
125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
150000001720 carbohydrates Chemical group 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
231100000504 carcinogenesis Toxicity 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
229960002376 chymotrypsin Drugs 0.000 description 1
239000003541 chymotrypsin inhibitor Substances 0.000 description 1
230000009918 complex formation Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 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
239000008121 dextrose Substances 0.000 description 1
125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 description 1
WOKPSXJEBSRSAT-UHFFFAOYSA-N dihydrobenzothiopyranyl sulfone group Chemical group S1C(CCC2=C1C=CC=C2)S(=O)(=O)C2SC1=C(CC2)C=CC=C1 WOKPSXJEBSRSAT-UHFFFAOYSA-N 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003118 drug derivative Substances 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000003792 electrolyte Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000000284 extract Substances 0.000 description 1
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
230000002390 hyperplastic effect Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229940100601 interleukin-6 Drugs 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
108010082117 matrigel Proteins 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
125000005010 perfluoroalkyl group Chemical group 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
239000003600 podophyllotoxin derivative Substances 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
229960002429 proline Drugs 0.000 description 1
125000001500 prolyl group Chemical class [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
201000005825 prostate adenocarcinoma Diseases 0.000 description 1
208000023958 prostate neoplasm Diseases 0.000 description 1
238000011471 prostatectomy Methods 0.000 description 1
235000019419 proteases Nutrition 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
239000011535 reaction buffer Substances 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
210000000582 semen Anatomy 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229960000187 tissue plasminogen activator Drugs 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
230000035899 viability Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Epidemiology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Zoology (AREA)
Urology & Nephrology (AREA)
Toxicology (AREA)
Gastroenterology & Hepatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Medicines Containing Plant Substances (AREA)

HR9718160.6A 1996-10-30 1997-10-24 Conjugates useful in the treatment of prostate canser HRP970566A2 (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US2922496P	1996-10-30	1996-10-30
GBGB9626309.0A GB9626309D0 (en)	1996-12-18	1996-12-18	Conjugates useful in the treatment of prostate cancer
US4292197P	1997-04-04	1997-04-04
GBGB9718160.6A GB9718160D0 (en)	1997-08-28	1997-08-28	Conjugates useful in the treatment of prostate cancer

Publications (1)

Publication Number	Publication Date
HRP970566A2 true HRP970566A2 (en)	1998-08-31

Family

ID=27451580

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR9718160.6A HRP970566A2 (en)	1996-10-30	1997-10-24	Conjugates useful in the treatment of prostate canser

Country Status (31)

Country	Link
EP (1)	EP0942754B1 (de)
JP (1)	JP2000509407A (de)
KR (1)	KR100508199B1 (de)
AR (1)	AR008907A1 (de)
AT (1)	ATE239509T1 (de)
AU (1)	AU726434B2 (de)
BG (1)	BG64768B1 (de)
BR (1)	BR9712589A (de)
CA (1)	CA2268738A1 (de)
CO (1)	CO4930281A1 (de)
CZ (1)	CZ155599A3 (de)
DE (1)	DE69721810T2 (de)
DK (1)	DK0942754T3 (de)
DZ (1)	DZ2333A1 (de)
EA (1)	EA002066B1 (de)
EE (1)	EE03858B1 (de)
ES (1)	ES2196374T3 (de)
HR (1)	HRP970566A2 (de)
HU (1)	HUP0000651A3 (de)
ID (1)	ID21358A (de)
IL (1)	IL129356A0 (de)
IS (1)	IS5025A (de)
NO (1)	NO992069L (de)
PE (1)	PE17399A1 (de)
PL (1)	PL333004A1 (de)
PT (1)	PT942754E (de)
SK (1)	SK57399A3 (de)
TR (1)	TR199901485T2 (de)
TW (1)	TW425286B (de)
WO (1)	WO1998018493A2 (de)
YU (1)	YU21399A (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HRP20000367A2 (en) *	1997-12-02	2000-12-31	Merck & Co Inc	Conjugates useful in the treatment of prostate cancer
CA2238257A1 (en) *	1998-05-22	1999-11-22	Universite De Montreal	Endocytosis of amf-r and uses thereof in cancer therapy
WO2000003737A2 (en) *	1998-07-17	2000-01-27	The United States Of America, Represented By The Secretary, Department Of Health And Human Services	Water-soluble drugs and methods for their production
US6174858B1 (en)	1998-11-17	2001-01-16	Merck & Co., Inc.	Conjugates useful in the treatment of prostate cancer
PT1144011E (pt) *	1998-12-11	2010-06-16	Coulter Pharm Inc	Compostos pró-fármacos e processo para a sua preparação
GB9924759D0 (en)	1999-10-19	1999-12-22	Merck Sharp & Dohme	Process for preparing peptide intermediates
WO2001028593A2 (en) *	1999-10-19	2001-04-26	Merck & Co., Inc.	Conjugates useful in the treatment of prostate cancer
JP2003512475A (ja) *	1999-10-27	2003-04-02	メルクエンドカムパニーインコーポレーテッド	前立腺癌の治療に有用な複合体の塩形態
HUP0300590A2 (hu) *	2000-03-15	2003-07-28	Bristol-Myers Squibb Pharma Company	Peptidázzal hasítható, célzott antineoplasztikus szerek és terápiás alkalmazásuk
EP2316468A1 (de) *	2002-02-22	2011-05-04	Shire LLC	Abgabesystem und Verfahren zum Schutz und zur Verabreichung von Dextroamphetamin
US20050187147A1 (en) *	2003-09-22	2005-08-25	Newman Michael J.	Compositions and methods for increasing drug efficiency
CN100372862C (zh) *	2003-11-05	2008-03-05	天津和美生物技术有限公司	具有抗癌活性的阿霉素衍生物及其制备方法和应用
WO2008067495A2 (en) *	2006-11-29	2008-06-05	Rutgers, The State University Of New Jersey	Chemotherapeutic conjugates and methods of use
CN101225094A (zh) *	2007-01-18	2008-07-23	天津和美生物技术有限公司	具有抗癌活性的蒽醌四环类化合物
AU2010223565B2 (en) *	2009-03-09	2016-06-23	Ktb Tumorforschungsgesellschaft Mbh	Prodrugs
JP6130307B2 (ja)	2011-03-17	2017-05-17	ザユニバーシティオブバーミンガム	再指向性免疫療法
CA2861066C (en)	2012-01-12	2024-01-02	Yale University	Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase
GB201203442D0 (en)	2012-02-28	2012-04-11	Univ Birmingham	Immunotherapeutic molecules and uses
GB201311888D0 (en)	2013-07-03	2013-08-14	Glaxosmithkline Ip Dev Ltd	Novel compounds
GB201311891D0 (en)	2013-07-03	2013-08-14	Glaxosmithkline Ip Dev Ltd	Novel compound
US20180228907A1 (en)	2014-04-14	2018-08-16	Arvinas, Inc.	Cereblon ligands and bifunctional compounds comprising the same
US10441649B2 (en)	2015-02-02	2019-10-15	The University Of Birmingham	Targeting moiety peptide epitope complexes having a plurality of T-cell epitopes
ES2873846T5 (en)	2015-11-19	2025-06-23	Revitope Ltd	Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells
CA3203072A1 (en)	2020-12-22	2022-06-30	Andrea CASAZZA	Compounds comprising a tetrapeptidic moiety
WO2022167664A1 (en)	2021-02-07	2022-08-11	Cobiores Nv	Compounds comprising a tetrapeptidic moiety

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6143864A (en) *	1994-06-28	2000-11-07	Merck & Co., Inc.	Peptides
US5866679A (en) *	1994-06-28	1999-02-02	Merck & Co., Inc.	Peptides
AU708475B2 (en) *	1995-10-18	1999-08-05	Merck & Co., Inc.	Conjugates useful in the treatment of benign prostatic hyperplasia

1997
- 1997-10-24 HR HR9718160.6A patent/HRP970566A2/hr not_active Application Discontinuation
- 1997-10-27 HU HU0000651A patent/HUP0000651A3/hu unknown
- 1997-10-27 CA CA002268738A patent/CA2268738A1/en not_active Abandoned
- 1997-10-27 AU AU51497/98A patent/AU726434B2/en not_active Ceased
- 1997-10-27 ES ES97946296T patent/ES2196374T3/es not_active Expired - Lifetime
- 1997-10-27 WO PCT/US1997/019225 patent/WO1998018493A2/en not_active Ceased
- 1997-10-27 IL IL12935697A patent/IL129356A0/xx not_active IP Right Cessation
- 1997-10-27 AT AT97946296T patent/ATE239509T1/de not_active IP Right Cessation
- 1997-10-27 EP EP97946296A patent/EP0942754B1/de not_active Expired - Lifetime
- 1997-10-27 PT PT97946296T patent/PT942754E/pt unknown
- 1997-10-27 YU YU21399A patent/YU21399A/sh unknown
- 1997-10-27 JP JP10520593A patent/JP2000509407A/ja not_active Ceased
- 1997-10-27 BR BR9712589-0A patent/BR9712589A/pt not_active Application Discontinuation
- 1997-10-27 ID IDW990259A patent/ID21358A/id unknown
- 1997-10-27 DK DK97946296T patent/DK0942754T3/da active
- 1997-10-27 EE EEP199900179A patent/EE03858B1/xx not_active IP Right Cessation
- 1997-10-27 EA EA199900428A patent/EA002066B1/ru not_active IP Right Cessation
- 1997-10-27 DE DE69721810T patent/DE69721810T2/de not_active Expired - Fee Related
- 1997-10-27 KR KR10-1999-7003846A patent/KR100508199B1/ko not_active Expired - Fee Related
- 1997-10-27 PL PL97333004A patent/PL333004A1/xx unknown
- 1997-10-27 TR TR1999/01485T patent/TR199901485T2/xx unknown
- 1997-10-27 CZ CZ991555A patent/CZ155599A3/cs unknown
- 1997-10-27 SK SK573-99A patent/SK57399A3/sk unknown
- 1997-10-28 CO CO97063170A patent/CO4930281A1/es unknown
- 1997-10-28 TW TW086115986A patent/TW425286B/zh not_active IP Right Cessation
- 1997-10-29 AR ARP970105032A patent/AR008907A1/es not_active Application Discontinuation
- 1997-10-29 DZ DZ970183A patent/DZ2333A1/xx active
- 1997-10-29 PE PE1997000970A patent/PE17399A1/es not_active Application Discontinuation
1999
- 1999-04-13 IS IS5025A patent/IS5025A/is unknown
- 1999-04-29 NO NO992069A patent/NO992069L/no not_active Application Discontinuation
- 1999-05-26 BG BG103436A patent/BG64768B1/bg unknown

Also Published As

Publication number	Publication date
PT942754E (pt)	2003-08-29
EA002066B1 (ru)	2001-12-24
NO992069D0 (no)	1999-04-29
IS5025A (is)	1999-04-13
CO4930281A1 (es)	2000-06-27
KR20000052970A (ko)	2000-08-25
ATE239509T1 (de)	2003-05-15
EE03858B1 (et)	2002-10-15
BG103436A (en)	2000-04-28
EP0942754B1 (de)	2003-05-07
AU5149798A (en)	1998-05-22
NO992069L (no)	1999-06-30
YU21399A (sh)	2000-03-21
AU726434B2 (en)	2000-11-09
DZ2333A1 (fr)	2002-12-28
IL129356A0 (en)	2000-02-17
EA199900428A1 (ru)	2000-02-28
WO1998018493A2 (en)	1998-05-07
HK1024876A1 (en)	2000-10-27
HUP0000651A2 (hu)	2000-06-28
DE69721810D1 (de)	2003-06-12
ID21358A (id)	1999-05-27
TW425286B (en)	2001-03-11
KR100508199B1 (ko)	2005-08-17
CZ155599A3 (cs)	1999-10-13
WO1998018493A3 (en)	1998-07-23
EP0942754A2 (de)	1999-09-22
ES2196374T3 (es)	2003-12-16
TR199901485T2 (xx)	1999-08-23
CA2268738A1 (en)	1998-05-07
SK57399A3 (en)	2000-01-18
DK0942754T3 (da)	2003-08-04
EE9900179A (et)	1999-12-15
HUP0000651A3 (en)	2001-12-28
PL333004A1 (en)	1999-11-08
PE17399A1 (es)	1999-02-20
AR008907A1 (es)	2000-02-23
BG64768B1 (bg)	2006-03-31
DE69721810T2 (de)	2004-03-11
JP2000509407A (ja)	2000-07-25
BR9712589A (pt)	1999-10-26

Legal Events

Date	Code	Title
1998-08-31	A1OB	Publication of a patent application
1999-01-12	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2005-02-16	OBST	Application withdrawn

Publication	Publication Date	Title
US5948750A (en)	1999-09-07	Conjugates useful in the treatment of prostate cancer
AU715632B2 (en)	2000-02-03	Conjugates useful in the treatment of prostate cancer
US6391305B1 (en)	2002-05-21	Conjugates useful in the treatment of prostate cancer
HRP970566A2 (en)	1998-08-31	Conjugates useful in the treatment of prostate canser
US5998362A (en)	1999-12-07	Conjugates useful in the treatment of prostate cancer
US20020103136A1 (en)	2002-08-01	Conjugates useful in the treatment of prostate cancer
EP0853483A1 (de)	1998-07-22	Neue peptide
EP1009420B1 (de)	2003-12-17	Konjugate welche bei der behandlung von prostatakrebs nützlich sind
US20030232760A1 (en)	2003-12-18	Conjugates useful in the treatment of prostate cancer
US6174858B1 (en)	2001-01-16	Conjugates useful in the treatment of prostate cancer
US20070244055A1 (en)	2007-10-18	Conjugates useful in the treatment of prostate cancer
AU744652B2 (en)	2002-02-28	Conjugates useful in the treatment of prostate cancer
US20020115596A1 (en)	2002-08-22	Conjugates useful in the treatment of prostate cancer
US6127333A (en)	2000-10-03	Conjugates useful in the treatment of prostate cancer
US20050119166A1 (en)	2005-06-02	Conjugates useful in the treatment of prostate cancer
WO1999044628A1 (en)	1999-09-10	Conjugates useful in the treatment of prostate cancer
MXPA00005434A (en)	2002-02-26	Conjugates useful in the treatment of prostate cancer