RU2474586C2 - Эффективные аналоги компстатина - Google Patents
Эффективные аналоги компстатина Download PDFInfo
- Publication number
- RU2474586C2 RU2474586C2 RU2008126232/04A RU2008126232A RU2474586C2 RU 2474586 C2 RU2474586 C2 RU 2474586C2 RU 2008126232/04 A RU2008126232/04 A RU 2008126232/04A RU 2008126232 A RU2008126232 A RU 2008126232A RU 2474586 C2 RU2474586 C2 RU 2474586C2
- Authority
- RU
- Russia
- Prior art keywords
- tryptophan
- peptide
- seq
- trp
- compstatin
- Prior art date
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- RDTRHBCZFDCUPW-KWICJJCGSA-N 2-[(4r,7s,10s,13s,19s,22s,25s,28s,31s,34r)-4-[[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-34-[[(2s,3s)-2-amino-3-methylpentanoyl]amino]-25-(3-amino-3-oxopropyl)-7-[3-(diaminomethylideneamino)propyl]-10,13-bis(1h-imidazol-5-ylmethyl)-19-(1h-indol Chemical class C([C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CSSC[C@@H](C(N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)NCC(=O)N[C@@H](CC=2NC=NC=2)C(=O)N1)C(C)C)C(C)C)=O)NC(=O)[C@@H](N)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)C1=CN=CN1 RDTRHBCZFDCUPW-KWICJJCGSA-N 0.000 title description 106
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 190
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- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 52
- 230000014509 gene expression Effects 0.000 claims description 27
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 25
- -1 Val Chemical compound 0.000 claims description 22
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- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 17
- ZADWXFSZEAPBJS-JTQLQIEISA-N 1-methyl-L-tryptophan Chemical compound C1=CC=C2N(C)C=C(C[C@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-JTQLQIEISA-N 0.000 claims description 16
- INPQIVHQSQUEAJ-VIFPVBQESA-N fluorotryptophane Chemical compound C1=C(F)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 INPQIVHQSQUEAJ-VIFPVBQESA-N 0.000 claims description 16
- ZADWXFSZEAPBJS-UHFFFAOYSA-N racemic N-methyl tryptophan Natural products C1=CC=C2N(C)C=C(CC(N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-UHFFFAOYSA-N 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 11
- HUNCSWANZMJLPM-UHFFFAOYSA-N 5-methyltryptophan Chemical compound CC1=CC=C2NC=C(CC(N)C(O)=O)C2=C1 HUNCSWANZMJLPM-UHFFFAOYSA-N 0.000 claims description 9
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- KRUDZOGZZBVSHD-JTQLQIEISA-N (2s)-2-azaniumyl-3-(1-formylindol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CN(C=O)C2=C1 KRUDZOGZZBVSHD-JTQLQIEISA-N 0.000 claims description 7
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- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 5
- KVNPSKDDJARYKK-JTQLQIEISA-N 5-methoxytryptophan Chemical compound COC1=CC=C2NC=C(C[C@H](N)C(O)=O)C2=C1 KVNPSKDDJARYKK-JTQLQIEISA-N 0.000 claims description 4
- KGVHCTWYMPWEGN-FSPLSTOPSA-N Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CN KGVHCTWYMPWEGN-FSPLSTOPSA-N 0.000 claims description 2
- VPZKQTYZIVOJDV-LMVFSUKVSA-N Thr-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(O)=O VPZKQTYZIVOJDV-LMVFSUKVSA-N 0.000 claims description 2
- DFTCYYILCSQGIZ-GCJQMDKQSA-N Thr-Ala-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O DFTCYYILCSQGIZ-GCJQMDKQSA-N 0.000 claims description 2
- UQTNIFUCMBFWEJ-IWGUZYHVSA-N Thr-Asn Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O UQTNIFUCMBFWEJ-IWGUZYHVSA-N 0.000 claims description 2
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| US10125171B2 (en) | 2011-05-11 | 2018-11-13 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| US10308687B2 (en) | 2013-03-15 | 2019-06-04 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| US10407466B2 (en) | 2005-10-08 | 2019-09-10 | Apellis Pharmaceuticals, Inc. | Methods of selecting compstatin mimetics |
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| US11510939B1 (en) | 2019-04-19 | 2022-11-29 | Apellis Pharmaceuticals, Inc. | RNAs for complement inhibition |
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| WO2022150260A1 (en) | 2021-01-05 | 2022-07-14 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| JP2024535850A (ja) | 2021-09-17 | 2024-10-02 | アルナイラム ファーマシューティカルズ， インコーポレイテッド | 補体成分（Ｃ３）をサイレンシングするためのｉＲＮＡ組成物および方法 |
| EP4423273A1 (en) | 2021-10-29 | 2024-09-04 | Alnylam Pharmaceuticals, Inc. | Complement factor b (cfb) irna compositions and methods of use thereof |
| CN114605495A (zh) * | 2022-04-20 | 2022-06-10 | 广州市乾相生物科技有限公司 | 一种乳四肽的合成方法 |
| WO2025176843A1 (en) | 2024-02-21 | 2025-08-28 | Ags Therapeutics Sas | Microalgae extracellular vesicle based gene therapy vectors (mev-gtvs), their preparation, and uses thereof |
| WO2025229200A1 (en) | 2024-05-03 | 2025-11-06 | Bachem Holding Ag | Manufacture of disulfide bonded peptides |
| CN119176856B (zh) * | 2024-11-22 | 2025-03-18 | 杭州诺泰诺和生物医药科技有限公司 | Pegcetacoplan的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004026328A1 (en) * | 2002-09-20 | 2004-04-01 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved activity |
| RU2238322C2 (ru) * | 1996-03-07 | 2004-10-20 | Имутран Лимитед | Протеин, обладающий способностью к образованию с3-конвертазы, днк, вектор, конъюгат и их использование |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2295746A1 (fr) * | 1974-12-23 | 1976-07-23 | Francaise Coop Pharma | Nouveaux derives du tryptophane a activite nerveuse centrale renforcee |
| IT1179866B (it) | 1984-12-12 | 1987-09-16 | Rotta Research Lab | Derivati del triptofano farmaceuticamente attivi e composizioni farmaceutiche che li contengono |
| US4576750A (en) | 1985-04-22 | 1986-03-18 | Merck & Co., Inc. | Tryptophan derivative |
| US5256642A (en) * | 1988-04-01 | 1993-10-26 | The Johns Hopkins University | Compositions of soluble complement receptor 1 (CR1) and a thrombolytic agent, and the methods of use thereof |
| US5167960A (en) * | 1988-08-03 | 1992-12-01 | New England Deaconess Hospital Corporation | Hirudin-coated biocompatible substance |
| AU7749491A (en) | 1990-04-23 | 1991-11-11 | Rijksuniversiteit Te Utrecht | Cyclic peptides and their use |
| WO1995023512A1 (en) | 1994-03-03 | 1995-09-08 | Alexion Pharmaceuticals, Inc. | Terminal complement inhibitor fusion genes and proteins |
| US5776970A (en) | 1994-04-28 | 1998-07-07 | Yeda Research And Development Co. Ltd. | Tryptophan derivatives as protein tyrosine kinase blockers and their use in the treatment of neoplastic diseases |
| JP2000505068A (ja) * | 1996-03-13 | 2000-04-25 | トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルベニア | 補体活性化を阻害する新規ペプチド類 |
| US6221621B1 (en) * | 1997-03-06 | 2001-04-24 | Bard Diagnostic Sciences, Inc. | Methods of screening for colorectal cancers in which a complement Factor I or related protein is associated |
| US6169057B1 (en) | 1997-09-04 | 2001-01-02 | The Regents Of The University Of California | Use of tryptophan and analogs as plant growth regulators |
| AU4648197A (en) | 1997-09-17 | 1999-04-05 | Burnham Institute, The | Peptides and peptidomimetics for inhibiting complement activation |
| AU3485999A (en) * | 1998-04-10 | 1999-11-01 | Mayo Foundation For Medical Education And Research | Neo-tryptophan |
| US7541032B2 (en) | 2002-09-20 | 2009-06-02 | Stichting Katholieke Universiteit | Antigen uptake receptor for Candida albicans on dendritic cells |
| JP5345849B2 (ja) * | 2005-10-08 | 2013-11-20 | ポテンシア ファーマシューティカルズ， インコーポレイテッド | 眼の障害のためのコンプスタチンおよびそのアナログ |
| EP1960422B1 (en) | 2005-11-28 | 2012-05-30 | The Trustees of The University of Pennsylvania | Potent compstatin analogs |
-
2006
- 2006-11-28 EP EP06844589A patent/EP1960422B1/en active Active
- 2006-11-28 CN CN2006800518175A patent/CN101400692B/zh active Active
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- 2013-04-23 JP JP2013090484A patent/JP5927139B2/ja active Active
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- 2015-03-24 IL IL237915A patent/IL237915B/en active IP Right Grant
- 2015-09-10 US US14/850,686 patent/US20160096866A1/en not_active Abandoned
-
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- 2017-04-18 US US15/490,437 patent/US20170305971A1/en not_active Abandoned
-
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- 2018-01-25 US US15/879,978 patent/US20190016758A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2238322C2 (ru) * | 1996-03-07 | 2004-10-20 | Имутран Лимитед | Протеин, обладающий способностью к образованию с3-конвертазы, днк, вектор, конъюгат и их использование |
| WO2004026328A1 (en) * | 2002-09-20 | 2004-04-01 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved activity |
Non-Patent Citations (4)
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10407466B2 (en) | 2005-10-08 | 2019-09-10 | Apellis Pharmaceuticals, Inc. | Methods of selecting compstatin mimetics |
| US11001610B2 (en) | 2011-05-11 | 2021-05-11 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| US10125171B2 (en) | 2011-05-11 | 2018-11-13 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| US11661441B2 (en) | 2011-05-11 | 2023-05-30 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| US11292815B2 (en) | 2012-11-15 | 2022-04-05 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| US10875893B2 (en) | 2012-11-15 | 2020-12-29 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| RU2705215C2 (ru) * | 2012-11-15 | 2019-11-06 | Апеллис Фармасьютикалс, Инк. | Клеточно-реактивные аналоги компстатина, аналоги компстатина длительного действия или аналоги компстатина нацеленного действия и связанные с ними композиции и способы |
| US10035822B2 (en) | 2012-11-15 | 2018-07-31 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| US10941184B2 (en) | 2013-03-15 | 2021-03-09 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| US10308687B2 (en) | 2013-03-15 | 2019-06-04 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| US11407789B2 (en) | 2013-03-15 | 2022-08-09 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| US11903994B2 (en) | 2015-10-07 | 2024-02-20 | Apellis Pharmaceuticals, Inc. | Dosing regimens |
| US11338013B2 (en) | 2016-10-17 | 2022-05-24 | Apellis Pharmaceuticals, Inc. | Combination therapy for C3 inhibition |
| US11040107B2 (en) | 2017-04-07 | 2021-06-22 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| US11844841B2 (en) | 2017-04-07 | 2023-12-19 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| US12290566B2 (en) | 2017-12-15 | 2025-05-06 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| US12458695B2 (en) | 2017-12-15 | 2025-11-04 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| US11510939B1 (en) | 2019-04-19 | 2022-11-29 | Apellis Pharmaceuticals, Inc. | RNAs for complement inhibition |
| US12251395B2 (en) | 2019-04-19 | 2025-03-18 | Apellis Pharmaceuticals, Inc. | RNAS for complement inhibition |
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