ES2677947T3 - Análogos potentes de la compstatina - Google Patents
Análogos potentes de la compstatina Download PDFInfo
- Publication number
- ES2677947T3 ES2677947T3 ES11001293.7T ES11001293T ES2677947T3 ES 2677947 T3 ES2677947 T3 ES 2677947T3 ES 11001293 T ES11001293 T ES 11001293T ES 2677947 T3 ES2677947 T3 ES 2677947T3
- Authority
- ES
- Spain
- Prior art keywords
- trp
- thr
- peptide
- tryptophan
- val
- 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.)
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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 137
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 202
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 59
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 33
- -1 Val Chemical compound 0.000 claims abstract description 30
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 16
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 15
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims abstract description 14
- 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 abstract description 13
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- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 13
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 7
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- 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 abstract 5
- 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 abstract 5
- 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 abstract 5
- 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 abstract 5
- 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 45
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- 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 abstract description 10
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- INPQIVHQSQUEAJ-UHFFFAOYSA-N 5-fluorotryptophan Chemical compound C1=C(F)C=C2C(CC(N)C(O)=O)=CNC2=C1 INPQIVHQSQUEAJ-UHFFFAOYSA-N 0.000 description 17
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- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 10
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- SNLOIIPRZGMRAB-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(1h-pyrrolo[2,3-b]pyridin-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H]([NH3+])C([O-])=O)=CNC2=N1 SNLOIIPRZGMRAB-QMMMGPOBSA-N 0.000 description 8
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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- C07—ORGANIC CHEMISTRY
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
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Landscapes
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| US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| HRP20120621T1 (hr) | 2005-11-28 | 2012-09-30 | The Trustees Of The University Of Pennsylvania | Sna“ni analozi kompstatina |
| US8637325B2 (en) * | 2009-02-16 | 2014-01-28 | University Of Wyoming | Method and apparatus for pyrolysis-induced cleavage in peptides and proteins |
| EP2083841B1 (en) * | 2006-10-20 | 2013-11-20 | Celldex Therapeutics, Inc. | SOLUBLE COMPLEMENT RECEPTOR TYPE I (sCR1) PROTEIN FOR USE IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION AND OTHER DISEASES OF THE EYE |
| HUE026001T2 (en) * | 2007-02-05 | 2016-04-28 | Apellis Pharmaceuticals Inc | Compstatin analogues for use in the treatment of the inflammatory condition 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 |
| US8563259B2 (en) | 2007-06-29 | 2013-10-22 | The Trustees Of The University Of Pennsylvania | Complement-mediated thrombophilic assay |
| EP2207530A4 (en) * | 2007-10-02 | 2013-09-11 | Potentia Pharmaceuticals Inc | DELAYED RELEASE OF COMPSTATIN ANALOG FROM GELEN |
| US20110190221A1 (en) * | 2008-03-28 | 2011-08-04 | Apellis Ag | Modulation and repletion/enhancement of the complement system for treatment of trauma |
| US8445190B2 (en) | 2008-09-30 | 2013-05-21 | The Trustees Of The University Of Pennsylvania | Method of inhibiting biomaterial-induced procoagulant activity using complement inhibitors |
| JP5882890B2 (ja) * | 2009-05-01 | 2016-03-09 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | ペプチド骨格およびｃ末端改変を持つ改変したコンプスタチン |
| US20110104154A1 (en) | 2009-10-30 | 2011-05-05 | Alcon Research, Ltd. | Single nucleotide polymorphisms and genes associated with age-related macular degeneration |
| US9358266B2 (en) | 2010-02-25 | 2016-06-07 | 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 |
| US20140113874A1 (en) * | 2010-09-23 | 2014-04-24 | 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 |
| US20140219999A1 (en) | 2011-04-01 | 2014-08-07 | The Trustees Of The University Of Pennsylvania | Treatment of colon cancer using complement inhibitors |
| DK2707384T3 (da) * | 2011-05-11 | 2022-06-07 | Apellis Pharmaceuticals Inc | Cellereaktiv, langtidsvirkende eller målrettede compstatinanaloger og anvendelser deraf |
| 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 |
| EP3524258B1 (en) | 2011-06-22 | 2025-10-01 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
| WO2013036778A2 (en) * | 2011-09-07 | 2013-03-14 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved pharmacokinetic properties |
| 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 |
| PT3660033T (pt) | 2012-11-15 | 2021-07-06 | Apellis Pharmaceuticals Inc | Análogos de compstatina de longa ação e composições e métodos relacionados |
| WO2014100407A1 (en) * | 2012-12-19 | 2014-06-26 | The Regents Of The University Of California | Compstatin analogs |
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| KR102736538B1 (ko) | 2013-12-12 | 2024-12-03 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 성분 ｉＲＮＡ 조성물 및 이의 이용 방법 |
| WO2015142701A1 (en) | 2014-03-17 | 2015-09-24 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved potency and pharmacokinetic properties |
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| FR2295746A1 (fr) | 1974-12-23 | 1976-07-23 | Francaise Coop Pharma | Nouveaux derives du tryptophane a activite nerveuse centrale renforcee |
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| GB9604865D0 (en) * | 1996-03-07 | 1996-05-08 | Imutran Ltd | Modified proteins |
| WO1997033603A1 (en) | 1996-03-13 | 1997-09-18 | Trustees Of The University Of Pennsylvania | Novel peptides which inhibit complement activation |
| 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 |
| US7989589B2 (en) | 2002-09-20 | 2011-08-02 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved activity |
| MX351152B (es) | 2005-10-08 | 2017-10-04 | Potentia Pharmaceuticals Inc | Compstatina y analogos de la misma para tratar trastornos oculares. |
| HRP20120621T1 (hr) | 2005-11-28 | 2012-09-30 | The Trustees Of The University Of Pennsylvania | Sna“ni analozi kompstatina |
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2006
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