CA2738091A1 - Bioactive pre-tubulysins and use thereof - Google Patents
Bioactive pre-tubulysins and use thereof Download PDFInfo
- Publication number
- CA2738091A1 CA2738091A1 CA2738091A CA2738091A CA2738091A1 CA 2738091 A1 CA2738091 A1 CA 2738091A1 CA 2738091 A CA2738091 A CA 2738091A CA 2738091 A CA2738091 A CA 2738091A CA 2738091 A1 CA2738091 A1 CA 2738091A1
- Authority
- CA
- Canada
- Prior art keywords
- tubulysin
- group
- cells
- microtubules
- compound
- 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.)
- Abandoned
Links
- 230000000975 bioactive effect Effects 0.000 title abstract description 4
- 229930184737 tubulysin Natural products 0.000 title description 24
- 150000001875 compounds Chemical class 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 30
- 108010060090 pretubulysin Proteins 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- -1 pre-tubulysin compound Chemical class 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
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- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
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- IUQKJKPHUBJDJV-UMNBWOBWSA-N (2s,4r)-2-methyl-4-[[2-[(3r)-4-methyl-3-[methyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-5-phenylpentanoic acid Chemical class N([C@@H]([C@@H](C)CC)C(=O)N(C)[C@H](CCC=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C IUQKJKPHUBJDJV-UMNBWOBWSA-N 0.000 abstract description 52
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
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- IBEDDHUHZBDXGB-OEJISELMSA-N Tubulysin A Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(O)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C IBEDDHUHZBDXGB-OEJISELMSA-N 0.000 description 27
- IBEDDHUHZBDXGB-UHFFFAOYSA-N Tubulysin A Natural products N=1C(C(=O)NC(CC(C)C(O)=O)CC=2C=CC(O)=CC=2)=CSC=1C(OC(C)=O)CC(C(C)C)N(COC(=O)CC(C)C)C(=O)C(C(C)CC)NC(=O)C1CCCCN1C IBEDDHUHZBDXGB-UHFFFAOYSA-N 0.000 description 27
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- 108010061212 tubulysin D Proteins 0.000 description 21
- SAJNCFZAPSBQTQ-UHFFFAOYSA-N tubulysin D Natural products N=1C(C(=O)NC(CC(C)C(O)=O)CC=2C=CC=CC=2)=CSC=1C(OC(C)=O)CC(C(C)C)N(COC(=O)CC(C)C)C(=O)C(C(C)CC)NC(=O)C1CCCCN1C SAJNCFZAPSBQTQ-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Crystallography & Structural Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08165147.3 | 2008-09-25 | ||
| EP08165147A EP2174947A1 (en) | 2008-09-25 | 2008-09-25 | Bioactive pre-tubulysins and use thereof |
| PCT/EP2009/062282 WO2010034724A1 (en) | 2008-09-25 | 2009-09-22 | Bioactive pre-tubulysins and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2738091A1 true CA2738091A1 (en) | 2010-04-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2738091A Abandoned CA2738091A1 (en) | 2008-09-25 | 2009-09-22 | Bioactive pre-tubulysins and use thereof |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8791098B2 (enExample) |
| EP (2) | EP2174947A1 (enExample) |
| JP (1) | JP2012503621A (enExample) |
| CA (1) | CA2738091A1 (enExample) |
| WO (1) | WO2010034724A1 (enExample) |
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| US8288557B2 (en) | 2004-07-23 | 2012-10-16 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| CN101678124A (zh) | 2007-03-14 | 2010-03-24 | 恩多塞特公司 | 结合配体连接的微管溶素递药缀合物 |
| CN101784565B (zh) | 2007-06-25 | 2014-12-10 | 恩多塞特公司 | 含有亲水性间隔区接头的共轭物 |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| US8394922B2 (en) | 2009-08-03 | 2013-03-12 | Medarex, Inc. | Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof |
| EP2409983A1 (en) | 2010-07-19 | 2012-01-25 | Leibniz-Institut für Pflanzenbiochemie (IPB) | Tubulysin analogues |
| EP3228325A1 (en) | 2011-06-10 | 2017-10-11 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
| WO2013126797A1 (en) | 2012-02-24 | 2013-08-29 | Purdue Research Foundation | Cholecystokinin b receptor targeting for imaging and therapy |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| HK1208216A1 (en) | 2012-05-15 | 2016-02-26 | Concortis Biosystems, Corp | Drug-conjugates, conjugation methods, and uses thereof |
| HUE048574T2 (hu) | 2012-07-12 | 2020-08-28 | Hangzhou Dac Biotech Co Ltd | Sejthez kötõdõ molekulák citotoxikus szerekkel képzett konjugátumai |
| AU2013331440A1 (en) | 2012-10-16 | 2015-04-30 | Endocyte, Inc. | Drug delivery conjugates containing unnatural amino acids and methods for using |
| CA2891280C (en) | 2012-11-24 | 2018-03-20 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules |
| AU2013359506B2 (en) | 2012-12-10 | 2018-05-24 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
| EP2931316B1 (en) | 2012-12-12 | 2019-02-20 | Mersana Therapeutics, Inc. | Hydroxyl-polymer-drug-protein conjugates |
| SI2956173T1 (sl) | 2013-02-14 | 2017-06-30 | Bristol-Myers Squibb Company | Spojine tubulizina, postopki pridobivanja in uporaba |
| US20160022829A1 (en) * | 2013-03-14 | 2016-01-28 | Mersana Therapeutics, Inc. | Tubulysin compounds and conjugates thereof |
| WO2015057585A1 (en) * | 2013-10-14 | 2015-04-23 | Regents Of The University Of Minnesota | Therapeutic compounds |
| CA3187392A1 (en) | 2013-10-15 | 2015-04-23 | Seagen Inc. | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
| AU2014337317A1 (en) | 2013-10-15 | 2016-09-15 | Sorrento Therapeutics Inc. | Drug-conjugates with a targeting molecule and two different drugs |
| CN106414465B (zh) | 2014-02-28 | 2021-11-16 | 杭州多禧生物科技有限公司 | 带电荷链接体及其在共轭反应上的应用 |
| US10077287B2 (en) | 2014-11-10 | 2018-09-18 | Bristol-Myers Squibb Company | Tubulysin analogs and methods of making and use |
| WO2016123412A1 (en) | 2015-01-28 | 2016-08-04 | Sorrento Therapeutics, Inc. | Antibody drug conjugates |
| KR20170137725A (ko) * | 2015-02-25 | 2017-12-13 | 윌리엄 마쉬 라이스 유니버시티 | 데스아세톡시투불리신 h 및 이의 유사체 |
| NZ739830A (en) | 2015-07-12 | 2021-12-24 | Hangzhou Dac Biotech Co Ltd | Bridge linkers for conjugation of cell-binding molecules |
| US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| MA43835A (fr) | 2016-03-25 | 2018-11-28 | Seattle Genetics Inc | Procédé de préparation de lieurs de médicaments pégylés et leurs intermédiaires |
| CN116143678A (zh) | 2016-11-14 | 2023-05-23 | 杭州多禧生物科技有限公司 | 偶联连接体，含有此连接体的细胞结合分子-药物偶联物及其制备和应用 |
| KR102648564B1 (ko) | 2017-03-24 | 2024-03-19 | 씨젠 인크. | 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물 |
| US11274124B2 (en) | 2017-11-29 | 2022-03-15 | William Marsh Rice University | Tubulysin analogues as anticancer agents and payloads for antibody-drug conjugates and methods of treatment therewith |
| MY208067A (en) | 2018-12-21 | 2025-04-11 | Regeneron Pharma | Tubulysins and protein-tubulysin conjugates |
| CN114040778A (zh) | 2019-06-29 | 2022-02-11 | 杭州多禧生物科技有限公司 | 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法 |
| CN111647040B (zh) * | 2020-05-11 | 2022-02-22 | 深圳市老年医学研究所 | 一种天然活性多肽Tubulysin U的制备方法 |
| WO2022078524A2 (en) | 2021-11-03 | 2022-04-21 | Hangzhou Dac Biotech Co., Ltd. | Specific conjugation of an antibody |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10254439A1 (de) * | 2002-11-21 | 2004-06-03 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Tubulysine, Herstellungsverfahren und Tubulysin-Mittel |
| US20100047841A1 (en) * | 2007-02-27 | 2010-02-25 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Synthesis of desacetoxytubulysin h and analogs thereof |
-
2008
- 2008-09-25 EP EP08165147A patent/EP2174947A1/en not_active Withdrawn
-
2009
- 2009-09-22 US US13/120,497 patent/US8791098B2/en not_active Expired - Fee Related
- 2009-09-22 JP JP2011528309A patent/JP2012503621A/ja active Pending
- 2009-09-22 WO PCT/EP2009/062282 patent/WO2010034724A1/en not_active Ceased
- 2009-09-22 EP EP09783296A patent/EP2331559A1/en not_active Withdrawn
- 2009-09-22 CA CA2738091A patent/CA2738091A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20110245295A1 (en) | 2011-10-06 |
| EP2331559A1 (en) | 2011-06-15 |
| US8791098B2 (en) | 2014-07-29 |
| WO2010034724A1 (en) | 2010-04-01 |
| EP2174947A1 (en) | 2010-04-14 |
| JP2012503621A (ja) | 2012-02-09 |
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| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20140826 |
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| FZDE | Discontinued |
Effective date: 20160922 |