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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (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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| WO2006012527A1 (en) | 2004-07-23 | 2006-02-02 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| AU2008224988A1 (en) | 2007-03-14 | 2008-09-18 | Endocyte, Inc. | Binding ligand linked drug delivery conjugates of tubulysins |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| RU2523909C2 (ru) | 2007-06-25 | 2014-07-27 | Эндосайт, Инк. | Конъюгаты, содержащие гидрофильные спейсеры линкеров |
| 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 |
| MX2013014583A (es) | 2011-06-10 | 2014-03-31 | Mersana Therapeutics Inc | Conjugados de proteina-polimero-farmaco. |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | 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 |
| EP2850059A4 (en) | 2012-05-15 | 2016-06-29 | Concortis Biosystems Corp | CONJUGATES OF MEDICATION, METHODS OF CONJUGATION AND USE THEREOF |
| US10501412B2 (en) | 2012-07-12 | 2019-12-10 | Hangzhou Dac Biotech Co., Ltd. | Conjugates of cell binding molecules with cytotoxic agents |
| WO2014062697A2 (en) | 2012-10-16 | 2014-04-24 | Endocyte, Inc. | Drug delivery conjugates containing unnatural amino acids and methods for using |
| JP6133431B2 (ja) | 2012-11-24 | 2017-05-24 | ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． | 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用 |
| JP6334553B2 (ja) | 2012-12-10 | 2018-05-30 | メルサナ セラピューティクス，インコーポレイティド | タンパク質−高分子−薬剤コンジュゲート |
| EP2931316B1 (en) | 2012-12-12 | 2019-02-20 | Mersana Therapeutics, Inc. | Hydroxyl-polymer-drug-protein conjugates |
| KR102215954B1 (ko) | 2013-02-14 | 2021-02-15 | 브리스톨-마이어스 스큅 컴퍼니 | 튜부리신 화합물, 그의 제조 및 사용 방법 |
| WO2014160360A1 (en) * | 2013-03-14 | 2014-10-02 | Mersana Therapeutics Inc. | Tubulysin compounds and conjugates thereof |
| WO2015057585A1 (en) * | 2013-10-14 | 2015-04-23 | Regents Of The University Of Minnesota | Therapeutic compounds |
| EP3756663A1 (en) | 2013-10-15 | 2020-12-30 | Seagen Inc. | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
| EP3057610B1 (en) | 2013-10-15 | 2021-09-22 | Sorrento Therapeutics, Inc. | Drug-conjugates with a targeting molecule and two different drugs |
| CA2938919C (en) | 2014-02-28 | 2020-12-29 | Hangzhou Dac Biotech Co., Ltd | Charged linkers and their uses for conjugation |
| US10077287B2 (en) | 2014-11-10 | 2018-09-18 | Bristol-Myers Squibb Company | Tubulysin analogs and methods of making and use |
| CA2975383C (en) | 2015-01-28 | 2023-09-12 | Sorrento Therapeutics, Inc. | Antibody drug conjugates comprising dolastatin derivatives |
| US10808007B2 (en) * | 2015-02-25 | 2020-10-20 | William Marsh Rice University | Desacetoxytubulysin H and analogs thereof |
| AU2015242213A1 (en) | 2015-07-12 | 2018-03-08 | 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 |
| MX2018006218A (es) | 2015-12-04 | 2018-09-05 | Seattle Genetics Inc | Conjugados de compuestos de tubulisina cuaternizada. |
| EA201892040A1 (ru) | 2016-03-25 | 2019-04-30 | Сиэтл Дженетикс, Инк. | Способ получения пегилированных соединений лекарственный препарат - линкер и их промежуточных соединений |
| MX2019005583A (es) | 2016-11-14 | 2019-10-21 | Hangzhou Dac Biotech Co Ltd | Vinculantes de conjugacion, conjugados de molecula de union a celulas que contienen los vinculantes, metodos de creacion y usos de dichos conjugados con los vinculantes. |
| MX2019010769A (es) | 2017-03-24 | 2019-12-11 | Seattle Genetics Inc | Proceso para la preparacion de enlazadores de farmacos de glucuronidos y compuestos intermediarios de los mismos. |
| WO2019108685A1 (en) | 2017-11-29 | 2019-06-06 | William March Rice University | Tubulysin analogues as anticancer agents and payloads for antibody-drug conjugates and methods of treatment therewith |
| WO2020132658A2 (en) | 2018-12-21 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | Tubulysins and protein-tubulysin conjugates |
| US20230025327A1 (en) | 2019-06-29 | 2023-01-26 | Hangzhou Dac Biotech Co., Ltd. | Conjugates of tubulysin derivatives and cell binding molecules and methods of making |
| 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 |
| CN117980327A (zh) | 2021-11-03 | 2024-05-03 | 杭州多禧生物科技有限公司 | 抗体的特异性偶联 |
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 |
| WO2008106080A2 (en) * | 2007-02-27 | 2008-09-04 | 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
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2009
- 2009-09-22 JP JP2011528309A patent/JP2012503621A/ja active Pending
- 2009-09-22 CA CA2738091A patent/CA2738091A1/en not_active Abandoned
- 2009-09-22 WO PCT/EP2009/062282 patent/WO2010034724A1/en not_active Ceased
- 2009-09-22 US US13/120,497 patent/US8791098B2/en not_active Expired - Fee Related
- 2009-09-22 EP EP09783296A patent/EP2331559A1/en not_active Withdrawn
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| Publication number | Publication date |
|---|---|
| US8791098B2 (en) | 2014-07-29 |
| EP2174947A1 (en) | 2010-04-14 |
| WO2010034724A1 (en) | 2010-04-01 |
| JP2012503621A (ja) | 2012-02-09 |
| EP2331559A1 (en) | 2011-06-15 |
| US20110245295A1 (en) | 2011-10-06 |
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| EEER | Examination request |
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| FZDE | Discontinued |
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