JP2014527070A5 - - Google Patents
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- JP2014527070A5 JP2014527070A5 JP2014528600A JP2014528600A JP2014527070A5 JP 2014527070 A5 JP2014527070 A5 JP 2014527070A5 JP 2014528600 A JP2014528600 A JP 2014528600A JP 2014528600 A JP2014528600 A JP 2014528600A JP 2014527070 A5 JP2014527070 A5 JP 2014527070A5
- Authority
- JP
- Japan
- Prior art keywords
- fap
- prodrug
- group
- lower alkyl
- proteasome inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229940002612 prodrug Drugs 0.000 claims description 36
- 239000000651 prodrug Substances 0.000 claims description 36
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 18
- 239000003207 proteasome inhibitor Substances 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 12
- 238000003776 cleavage reaction Methods 0.000 claims description 11
- 230000007017 scission Effects 0.000 claims description 11
- 239000013543 active substance Substances 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 210000002536 stromal cell Anatomy 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000004913 activation Effects 0.000 claims description 6
- 229940127089 cytotoxic agent Drugs 0.000 claims description 6
- 210000002950 fibroblast Anatomy 0.000 claims description 6
- 241000282326 Felis catus Species 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 102000056251 Prolyl Oligopeptidases Human genes 0.000 claims description 5
- 102100037838 Prolyl endopeptidase Human genes 0.000 claims description 5
- 101710178372 Prolyl endopeptidase Proteins 0.000 claims description 5
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 claims description 5
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 230000002797 proteolythic effect Effects 0.000 claims description 3
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 230000028327 secretion Effects 0.000 claims description 2
- 231100000331 toxic Toxicity 0.000 claims description 2
- 230000002588 toxic effect Effects 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 15
- 150000001875 compounds Chemical class 0.000 claims 11
- 239000008194 pharmaceutical composition Substances 0.000 claims 9
- 210000004027 cell Anatomy 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims 6
- 230000000903 blocking effect Effects 0.000 claims 5
- 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 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000000623 heterocyclic group Chemical group 0.000 claims 4
- 230000002401 inhibitory effect Effects 0.000 claims 4
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims 3
- 125000002252 acyl group Chemical group 0.000 claims 3
- 125000000539 amino acid group Chemical group 0.000 claims 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims 2
- 238000001574 biopsy Methods 0.000 claims 2
- 229960004562 carboplatin Drugs 0.000 claims 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
- 229960003668 docetaxel Drugs 0.000 claims 2
- 229960004679 doxorubicin Drugs 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 125000000524 functional group Chemical group 0.000 claims 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 2
- 229960005277 gemcitabine Drugs 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 230000002209 hydrophobic effect Effects 0.000 claims 2
- -1 methoxysuccinyl Chemical group 0.000 claims 2
- 230000035699 permeability Effects 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- FWPWHHUJACGNMZ-NBBQQVJHSA-N (1s,2r,5r)-5-[(1s)-1-hydroxy-2-methylpropyl]-2-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound N1C(=O)[C@H](C)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C FWPWHHUJACGNMZ-NBBQQVJHSA-N 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 1
- 208000031886 HIV Infections Diseases 0.000 claims 1
- 208000037357 HIV infectious disease Diseases 0.000 claims 1
- 101001136986 Homo sapiens Proteasome subunit beta type-8 Proteins 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010062016 Immunosuppression Diseases 0.000 claims 1
- 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 1
- 241000124008 Mammalia Species 0.000 claims 1
- 108010064641 ONX 0912 Proteins 0.000 claims 1
- 108010079844 PR-957 Proteins 0.000 claims 1
- KMXHEXRPYSXLRN-JDVQERKKSA-N PS-519 Chemical compound N1C(=O)[C@H](CCC)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C KMXHEXRPYSXLRN-JDVQERKKSA-N 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- 102100035760 Proteasome subunit beta type-8 Human genes 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- ZYJKONDZYOWOHE-UHFFFAOYSA-N [4-amino-3-(hydroxymethyl)phenyl]methanol Chemical compound NC1=CC=C(CO)C=C1CO ZYJKONDZYOWOHE-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000030741 antigen processing and presentation Effects 0.000 claims 1
- 108010044540 auristatin Proteins 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 125000003180 beta-lactone group Chemical group 0.000 claims 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 1
- 229960001467 bortezomib Drugs 0.000 claims 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 claims 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- SJFBTAPEPRWNKH-CCKFTAQKSA-N delanzomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)C1=CC=CC(C=2C=CC=CC=2)=N1 SJFBTAPEPRWNKH-CCKFTAQKSA-N 0.000 claims 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims 1
- 229960003957 dexamethasone Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 108700002672 epoxomicin Proteins 0.000 claims 1
- DOGIDQKFVLKMLQ-JTHVHQAWSA-N epoxomicin Chemical compound CC[C@H](C)[C@H](N(C)C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1 DOGIDQKFVLKMLQ-JTHVHQAWSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229960002949 fluorouracil Drugs 0.000 claims 1
- 210000005260 human cell Anatomy 0.000 claims 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 229960003685 imatinib mesylate Drugs 0.000 claims 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 claims 1
- 230000001506 immunosuppresive effect Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000001678 irradiating effect Effects 0.000 claims 1
- MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 claims 1
- MBOMYENWWXQSNW-AWEZNQCLSA-N ixazomib citrate Chemical compound N([C@@H](CC(C)C)B1OC(CC(O)=O)(CC(O)=O)C(=O)O1)C(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MBOMYENWWXQSNW-AWEZNQCLSA-N 0.000 claims 1
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims 1
- 229960004942 lenalidomide Drugs 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- SWZXEVABPLUDIO-WSZYKNRRSA-N n-[(2s)-3-methoxy-1-[[(2s)-3-methoxy-1-[[(2s)-1-[(2r)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide Chemical compound N([C@@H](COC)C(=O)N[C@@H](COC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)[C@]1(C)OC1)C(=O)C1=CN=C(C)S1 SWZXEVABPLUDIO-WSZYKNRRSA-N 0.000 claims 1
- 229950005750 oprozomib Drugs 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 229960005079 pemetrexed Drugs 0.000 claims 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims 1
- 125000001151 peptidyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004437 phosphorous atom Chemical group 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 230000008093 supporting effect Effects 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
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 1
- 0 CC(C)[C@@](C([C@@]([C@]1C)O2)(C2=O)NC1=O)O* Chemical compound CC(C)[C@@](C([C@@]([C@]1C)O2)(C2=O)NC1=O)O* 0.000 description 2
- FTCFXJNXQMLMCC-ZQQDZYSUSA-N CC(C)C[C@@H](/C=C/S(C)(=O)=O)NC([C@H](CC(C)C)NC([C@H](CC(C)C)NC)=O)=O Chemical compound CC(C)C[C@@H](/C=C/S(C)(=O)=O)NC([C@H](CC(C)C)NC([C@H](CC(C)C)NC)=O)=O FTCFXJNXQMLMCC-ZQQDZYSUSA-N 0.000 description 1
- SHFYIABOLDVYDL-XEVUQIKYSA-N CC(C)C[C@@H](B(OC(CC(O)=O)C1C(O)=O)OC1=O)NC(CNC)=O Chemical compound CC(C)C[C@@H](B(OC(CC(O)=O)C1C(O)=O)OC1=O)NC(CNC)=O SHFYIABOLDVYDL-XEVUQIKYSA-N 0.000 description 1
- YVEKBPJIQYLZDU-KTUBMRJJSA-N CC(C)C[C@@H](C([C@]1(C)OC1)=O)NC(CNC(C(CC(C)C)NC([C@H](CCc1ccccc1)NC)=O)=O)=O Chemical compound CC(C)C[C@@H](C([C@]1(C)OC1)=O)NC(CNC(C(CC(C)C)NC([C@H](CCc1ccccc1)NC)=O)=O)=O YVEKBPJIQYLZDU-KTUBMRJJSA-N 0.000 description 1
- HEZVRGZEVQVONT-VRKAVTRVSA-N CC(C)[C@@H]([C@@]([C@H]([C@H]1C)OC)(C(SC[C@@H](C(O)=O)NC(C)=O)=O)NC1=O)O Chemical compound CC(C)[C@@H]([C@@]([C@H]([C@H]1C)OC)(C(SC[C@@H](C(O)=O)NC(C)=O)=O)NC1=O)O HEZVRGZEVQVONT-VRKAVTRVSA-N 0.000 description 1
- RMAVNBWCMCLWKH-GJZGRUSLSA-N CCN[C@@H](Cc1ccccc1)C(N[C@H](B(O)O)CC(C)C)=O Chemical compound CCN[C@@H](Cc1ccccc1)C(N[C@H](B(O)O)CC(C)C)=O RMAVNBWCMCLWKH-GJZGRUSLSA-N 0.000 description 1
- JRUYKTCURFJCJI-DDASBUEYSA-N CC[C@H](C)[C@@H]([C@H](C(N[C@@H]1[C@@H](C[C@@H](C(O)=O)NC([C@H](C)NC)=O)C1)=O)O1)C1=O Chemical compound CC[C@H](C)[C@@H]([C@H](C(N[C@@H]1[C@@H](C[C@@H](C(O)=O)NC([C@H](C)NC)=O)C1)=O)O1)C1=O JRUYKTCURFJCJI-DDASBUEYSA-N 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161528824P | 2011-08-30 | 2011-08-30 | |
| US61/528,824 | 2011-08-30 | ||
| PCT/US2012/053140 WO2013033396A2 (en) | 2011-08-30 | 2012-08-30 | Fap-activated proteasome inhibitors for treating solid tumors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017170106A Division JP2018016629A (ja) | 2011-08-30 | 2017-09-05 | 固形腫瘍を治療するためのｆａｐ活性化プロテアソーム阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014527070A JP2014527070A (ja) | 2014-10-09 |
| JP2014527070A5 true JP2014527070A5 (enExample) | 2015-10-15 |
| JP6207509B2 JP6207509B2 (ja) | 2017-10-04 |
Family
ID=47757170
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014528600A Active JP6207509B2 (ja) | 2011-08-30 | 2012-08-30 | 固形腫瘍を治療するためのｆａｐ活性化プロテアソーム阻害剤 |
| JP2017170106A Pending JP2018016629A (ja) | 2011-08-30 | 2017-09-05 | 固形腫瘍を治療するためのｆａｐ活性化プロテアソーム阻害剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017170106A Pending JP2018016629A (ja) | 2011-08-30 | 2017-09-05 | 固形腫瘍を治療するためのｆａｐ活性化プロテアソーム阻害剤 |
Country Status (14)
| Country | Link |
|---|---|
| US (6) | US9597410B2 (enExample) |
| EP (2) | EP2753334B1 (enExample) |
| JP (2) | JP6207509B2 (enExample) |
| CN (2) | CN103945856A (enExample) |
| AU (2) | AU2012301810B2 (enExample) |
| CA (1) | CA2846852C (enExample) |
| DK (1) | DK2753334T3 (enExample) |
| ES (1) | ES2929179T3 (enExample) |
| HR (1) | HRP20221320T1 (enExample) |
| HU (1) | HUE060305T2 (enExample) |
| PL (1) | PL2753334T3 (enExample) |
| PT (1) | PT2753334T (enExample) |
| SI (1) | SI2753334T1 (enExample) |
| WO (1) | WO2013033396A2 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE060305T2 (hu) | 2011-08-30 | 2023-02-28 | Tufts College | FAP-aktivált proteaszóma inhibitorok a szolid tumorok kezelésére |
| CA2893239A1 (en) * | 2012-12-03 | 2014-06-12 | F. Hoffmann-La Roche Ag | Substituted triazole and imidazole compounds |
| EP3008212A4 (en) * | 2013-06-10 | 2017-05-24 | Millennium Pharmaceuticals, Inc. | Methods of treatment of cancer |
| WO2015076359A1 (ja) * | 2013-11-21 | 2015-05-28 | 国立大学法人北海道大学 | プロテアソーム阻害性化合物 |
| US9737556B2 (en) | 2014-06-13 | 2017-08-22 | Trustees Of Tufts College | FAP-activated therapeutic agents, and uses related thereto |
| IL249370B (en) | 2014-06-13 | 2022-06-01 | Tufts College | Fap-activated therapeutic agents, and uses related thereto |
| AU2015282627B2 (en) | 2014-06-30 | 2020-04-02 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
| ES2704056T3 (es) | 2014-07-14 | 2019-03-14 | Centrax Int Inc | Compuestos de epoxicetona para la inhibición de enzimas |
| AU2015306574B2 (en) | 2014-08-22 | 2020-07-23 | Yafei Shanghai Biology Medicine Science & Technology Co. Ltd. | Specifically activated micromolecular target coupling body in tumor microenvironment and use thereof |
| CN104231047B (zh) * | 2014-08-22 | 2017-06-16 | 亚飞（上海）生物医药科技有限公司 | 水溶性靶向激活的紫杉醇衍生物及其制备和用途 |
| US10675364B2 (en) * | 2015-06-23 | 2020-06-09 | The Board Of Trustees Of The Leland Stanford Junior University | Rhodol fluorophores for near-infrared imaging |
| CN106588965A (zh) | 2015-10-15 | 2017-04-26 | 北京大学 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
| CN105938123B (zh) * | 2015-12-18 | 2018-09-14 | 重庆两江药物研发中心有限公司 | 一种卡非佐米中间体中杂质的检测方法 |
| EP3426674A4 (en) | 2016-03-09 | 2019-08-14 | Blade Therapeutics, Inc. | CYCLIC KETO AMID COMPOUNDS AS CALPAIN MODULATORS AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| JP7164521B2 (ja) | 2016-06-21 | 2022-11-01 | オリオン・オフサルモロジー・エルエルシー | 炭素環式プロリンアミド誘導体 |
| MX392422B (es) | 2016-06-21 | 2025-03-24 | Orion Ophthalmology LLC | Derivados de prolinamida heterociclica |
| US11292801B2 (en) | 2016-07-05 | 2022-04-05 | Blade Therapeutics, Inc. | Calpain modulators and therapeutic uses thereof |
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2012
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- 2012-08-30 DK DK12827686.2T patent/DK2753334T3/da active
- 2012-08-30 AU AU2012301810A patent/AU2012301810B2/en active Active
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- 2012-08-30 JP JP2014528600A patent/JP6207509B2/ja active Active
- 2012-08-30 SI SI201232012T patent/SI2753334T1/sl unknown
- 2012-08-30 EP EP12827686.2A patent/EP2753334B1/en active Active
- 2012-08-30 ES ES12827686T patent/ES2929179T3/es active Active
- 2012-08-30 PT PT128276862T patent/PT2753334T/pt unknown
- 2012-08-30 CN CN201280052940.4A patent/CN103945856A/zh active Pending
- 2012-08-30 CN CN201810059355.6A patent/CN108383893A/zh active Pending
- 2012-08-30 WO PCT/US2012/053140 patent/WO2013033396A2/en not_active Ceased
- 2012-08-30 US US14/241,666 patent/US9597410B2/en active Active
- 2012-08-30 EP EP22201696.6A patent/EP4144354B1/en active Active
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2018
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