PT1960422E - Análogos de compstatina potentes - Google Patents
Análogos de compstatina potentes Download PDFInfo
- Publication number
- PT1960422E PT1960422E PT06844589T PT06844589T PT1960422E PT 1960422 E PT1960422 E PT 1960422E PT 06844589 T PT06844589 T PT 06844589T PT 06844589 T PT06844589 T PT 06844589T PT 1960422 E PT1960422 E PT 1960422E
- Authority
- PT
- Portugal
- Prior art keywords
- trp
- peptide
- seq
- tryptophan
- 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 119
- 230000003389 potentiating effect Effects 0.000 title description 3
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- 230000000694 effects Effects 0.000 claims description 89
- 230000027455 binding Effects 0.000 claims description 49
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical class C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 28
- 230000014509 gene expression Effects 0.000 claims description 28
- -1 Val Chemical compound 0.000 claims description 23
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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 16
- 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 15
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
- 238000003556 assay Methods 0.000 claims description 14
- 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 14
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- 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 10
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- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 9
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
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- 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 6
- 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 4
- 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 4
- 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 4
- 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 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Landscapes
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| US7989589B2 (en) * | 2002-09-20 | 2011-08-02 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved activity |
| US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| ES2390828T3 (es) | 2005-11-28 | 2012-11-16 | The Trustees Of The University Of Pennsylvania | Análogos potentes de la compstatina |
| US8637325B2 (en) * | 2009-02-16 | 2014-01-28 | University Of Wyoming | Method and apparatus for pyrolysis-induced cleavage in peptides and proteins |
| CA2666843C (en) * | 2006-10-20 | 2015-06-16 | Celldex Therapeutics, Inc. | Treatment of age-related macular degeneration and other diseases of the eye |
| EP2148691B1 (en) * | 2007-02-05 | 2015-05-20 | Apellis Pharmaceuticals, Inc. | Compstatin analogues for use in the treatment of inflammatory conditions of the respiratory system |
| JP2009003429A (ja) * | 2007-05-18 | 2009-01-08 | Panasonic Corp | アクチュエータ |
| WO2008153963A1 (en) * | 2007-06-08 | 2008-12-18 | The Trustees Of The University Of Pennsylvania | Structure of compstatin-c3 complex and use for rational drug design |
| WO2009005651A2 (en) | 2007-06-29 | 2009-01-08 | The Trustees Of The University Of Pennsylvania | Complement-mediated thrombophilic assay |
| CA2701470A1 (en) * | 2007-10-02 | 2009-04-09 | Potentia Pharmaceuticals, Inc. | Sustained delivery of compstatin analogs from gels |
| WO2009121065A2 (en) * | 2008-03-28 | 2009-10-01 | Apellis Ag | Modulation and repletion/enhancement of the complement system for treatment of trauma |
| WO2010039690A1 (en) * | 2008-09-30 | 2010-04-08 | The Trustees Of The University Of Pennsylvania | Method of inhibiting biomaterial-induced procoagulant activity using complement inhibitors |
| CA2760839C (en) * | 2009-05-01 | 2019-02-12 | The Trustees Of The University Of Pennsylvania | Modified compstatin with peptide backbone and c-terminal modifications |
| US20110104154A1 (en) | 2009-10-30 | 2011-05-05 | Alcon Research, Ltd. | Single nucleotide polymorphisms and genes associated with age-related macular degeneration |
| WO2011106635A1 (en) | 2010-02-25 | 2011-09-01 | The Trustees Of The University Of Pennsylvania | Treatment of sepsis using complement inhibitors |
| US9421240B2 (en) | 2010-06-22 | 2016-08-23 | Apellis Pharmaceuticals, Inc. | Compstatin analogs for treatment of neuropathic pain |
| CA2813049A1 (en) | 2010-09-23 | 2012-03-29 | The Trustees Of The University Of Pennsylvania | Modified compstatin with improved stability and binding properties |
| BR112013007442A2 (pt) * | 2010-09-28 | 2019-09-24 | Amylin Pharmaceuticals Llc | polipeptídeos construídos tendo duração de ação realçada |
| WO2012095519A1 (en) | 2011-01-13 | 2012-07-19 | Leibniz-Institut Für Naturstoff-Forschung Und Infektionsbiologie | Potent inhibitors of complement activation |
| WO2012135624A1 (en) | 2011-04-01 | 2012-10-04 | The Trustees Of The University Of Pennsylvania | Treatment of colon cancer using complement inhibitors |
| RU2653439C9 (ru) | 2011-05-11 | 2018-10-16 | Апеллис Фармасьютикалс, Инк. | Клеточно-реактивные аналоги компстатина, аналоги компстатина длительного действия или аналоги компстатина нацеленного действия и их применение |
| WO2012162215A1 (en) | 2011-05-20 | 2012-11-29 | The Trustees Of The University Of Pennsylvania | Promotion of fracture healing using complement inhibitors |
| WO2012174055A1 (en) | 2011-06-13 | 2012-12-20 | The Trustees Of The University Of Pennsylvania | Wound healing using complement inhibitors |
| CA2840270C (en) | 2011-06-22 | 2023-09-26 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
| PL2753636T3 (pl) * | 2011-09-07 | 2020-05-18 | The Trustees Of The University Of Pennsylvania | Analogi kompstatyny o ulepszonych właściwościach farmakokinetycznych |
| WO2014028861A1 (en) * | 2012-08-17 | 2014-02-20 | Apellis Pharmaceuticals, Inc. | Detection of high risk drusen |
| WO2014078734A2 (en) * | 2012-11-15 | 2014-05-22 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| US10035822B2 (en) * | 2012-11-15 | 2018-07-31 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| WO2014100407A1 (en) * | 2012-12-19 | 2014-06-26 | The Regents Of The University Of California | Compstatin analogs |
| WO2014152391A1 (en) | 2013-03-15 | 2014-09-25 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
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| US10213476B2 (en) | 2014-03-17 | 2019-02-26 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved potency and pharmacokinetic properties |
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| AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
| KR20180090785A (ko) | 2015-10-07 | 2018-08-13 | 아펠리스 파마슈티컬스 인코포레이티드 | 투여 요법 |
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| BR112019020955A2 (pt) | 2017-04-07 | 2020-05-05 | Apellis Pharmaceuticals, Inc. | regimes de dosagem e composições e métodos relacionados |
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| BR112020017385A2 (pt) | 2018-02-27 | 2020-12-15 | Zp Spv 3 K/S | Análogos de compstatina, métodos e seus usos médicos |
| HUE057693T2 (hu) | 2018-04-06 | 2022-05-28 | Univ Pennsylvania | Fokozott oldhatóságú és javított farmakokinetikai tulajdonságú kompsztatin analógok |
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| CN113195472A (zh) | 2018-12-17 | 2021-07-30 | 艾其林医药公司 | 用于治疗补体介导的病症的靶向给药 |
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| 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 |
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| 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 |
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| US20260234189A1 (en) | 2025-01-24 | 2026-08-13 | Boehringer Ingelheim International Gmbh | Novel and stable compstatin analogues |
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| 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 |
| WO1991016345A1 (en) | 1990-04-23 | 1991-10-31 | Rijksuniversiteit Te Utrecht | Cyclic peptides and their use |
| CA2184356A1 (en) | 1994-03-03 | 1995-09-08 | Russell P. Rother | 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 |
| GB9604865D0 (en) * | 1996-03-07 | 1996-05-08 | Imutran Ltd | Modified proteins |
| 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 |
| WO1999013899A1 (en) | 1997-09-17 | 1999-03-25 | Trustees Of The University Of Pennsylvania | Peptides and peptidomimetics for inhibiting complement activation |
| US6214790B1 (en) | 1998-04-10 | 2001-04-10 | Mayo Foundation For Medical Education And Research | Neo-tryptophan |
| US7989589B2 (en) * | 2002-09-20 | 2011-08-02 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved activity |
| US7541032B2 (en) | 2002-09-20 | 2009-06-02 | Stichting Katholieke Universiteit | Antigen uptake receptor for Candida albicans on dendritic cells |
| CN101325963B (zh) * | 2005-10-08 | 2016-01-27 | 博泰迪亚制药公司 | 用于眼部病症的补体抑制素和其类似物 |
| ES2390828T3 (es) | 2005-11-28 | 2012-11-16 | The Trustees Of The University Of Pennsylvania | Análogos potentes de la compstatina |
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