CA2807685C - P53 derived peptidomimetic macrocycle - Google Patents
P53 derived peptidomimetic macrocycle Download PDFInfo
- Publication number
- CA2807685C CA2807685C CA2807685A CA2807685A CA2807685C CA 2807685 C CA2807685 C CA 2807685C CA 2807685 A CA2807685 A CA 2807685A CA 2807685 A CA2807685 A CA 2807685A CA 2807685 C CA2807685 C CA 2807685C
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- Prior art keywords
- peptidomimetic macrocycle
- amino acid
- alkyl
- independently
- ltf
- 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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Classifications
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/52—Cyclic peptides containing at least one abnormal peptide link with only normal peptide links in the ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
- C07K14/4746—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used p53
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
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Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Biophysics (AREA)
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- Immunology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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| US37370110P | 2010-08-13 | 2010-08-13 | |
| US37363810P | 2010-08-13 | 2010-08-13 | |
| US61/373,638 | 2010-08-13 | ||
| US61/373,701 | 2010-08-13 | ||
| US37416310P | 2010-08-16 | 2010-08-16 | |
| US61/374,163 | 2010-08-16 | ||
| PCT/US2011/047692 WO2012021876A2 (en) | 2010-08-13 | 2011-08-13 | Peptidomimetic macrocycles |
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| CA2807685A1 CA2807685A1 (en) | 2012-02-16 |
| CA2807685C true CA2807685C (en) | 2020-10-06 |
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| CA2807685A Active CA2807685C (en) | 2010-08-13 | 2011-08-13 | P53 derived peptidomimetic macrocycle |
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| US (5) | US8859723B2 (OSRAM) |
| EP (1) | EP2603600B1 (OSRAM) |
| JP (3) | JP2013535514A (OSRAM) |
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| SI (1) | SI2603600T1 (OSRAM) |
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| CN105061577A (zh) | 2006-12-14 | 2015-11-18 | 爱勒让治疗公司 | 双巯基大环化系统 |
| CA2677045C (en) | 2007-01-31 | 2016-10-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| CN104086641A (zh) | 2007-02-23 | 2014-10-08 | 爱勒让治疗公司 | 三唑大环系统 |
| CA2682174C (en) | 2007-03-28 | 2021-04-06 | President And Fellows Of Harvard College | Stitched polypeptides |
| CA2737922A1 (en) | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2743177A1 (en) | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| US9175047B2 (en) | 2009-01-14 | 2015-11-03 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| AU2010298338A1 (en) | 2009-09-22 | 2012-04-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2011047215A1 (en) * | 2009-10-14 | 2011-04-21 | Aileron Therapeutics, Inc. | Improved peptidomimetic macrocycles |
| NZ600157A (en) * | 2009-12-22 | 2013-07-26 | Takeda Pharmaceutical | Sustained-release formulation comprising metastin derivative |
| FR2956115B1 (fr) | 2010-02-05 | 2012-04-06 | Isp Investments Inc | Nouveaux peptides activateurs de la caspase-14 et compositions les comprenant |
| WO2012021875A1 (en) | 2010-08-13 | 2012-02-16 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with triazole linkers |
| CN108929375A (zh) | 2011-10-18 | 2018-12-04 | 爱勒让治疗公司 | 拟肽大环化合物 |
| CN112500466B (zh) | 2012-02-15 | 2022-05-03 | 艾瑞朗医疗公司 | 拟肽大环化合物 |
| CA2864120A1 (en) * | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| WO2014055039A1 (en) * | 2012-10-01 | 2014-04-10 | Agency For Science, Technology And Research | Peptides and methods for treating cancer |
| CN104812384B (zh) | 2012-11-01 | 2020-09-18 | 爱勒让治疗公司 | 二取代的氨基酸及其制备和使用方法 |
| WO2014138429A2 (en) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating hif1alpha |
| WO2014205317A2 (en) * | 2013-06-20 | 2014-12-24 | California Institute Of Technology | Cyclic peptides as protein targeting agents |
| WO2015153761A2 (en) | 2014-04-02 | 2015-10-08 | University Of Rochester | Macrocyclic peptidomimetics for alpha-helix mimicry |
| US20170037086A1 (en) * | 2014-04-09 | 2017-02-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with pth activity |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| EP3197478A4 (en) * | 2014-09-24 | 2018-05-30 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| SG11201707750YA (en) | 2015-03-20 | 2017-10-30 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US9765117B2 (en) | 2015-08-24 | 2017-09-19 | Romek Figa | Peptides for treating cancer |
| EP3344275B8 (en) * | 2015-09-03 | 2023-04-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN108368161A (zh) | 2015-09-10 | 2018-08-03 | 艾瑞朗医疗公司 | 作为mcl-1调节剂的拟肽大环化合物 |
| AU2016347456B2 (en) | 2015-10-27 | 2018-12-13 | F. Hoffmann-La Roche Ag | Peptide macrocycles against acinetobacter baumannii |
| EP3430031B1 (en) * | 2016-03-15 | 2021-10-20 | IDP Discovery Pharma, S.L. | Peptides with anti-cancer activity |
| KR20180128022A (ko) * | 2016-03-21 | 2018-11-30 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드 모방 거대고리에 대한 동반 진단 도구 |
| EP3388444A1 (en) | 2017-04-10 | 2018-10-17 | F. Hoffmann-La Roche AG | Anti-bacterial peptide macrocycles and use thereof |
| WO2019020649A1 (en) * | 2017-07-25 | 2019-01-31 | Idp Discovery Pharma, S.L. | Anticancer peptides |
| US11865181B2 (en) | 2017-11-03 | 2024-01-09 | Yale University | Peptidic materials that traffic efficiently to the cell cytosol and nucleus |
| WO2019133179A2 (en) * | 2017-12-01 | 2019-07-04 | Massachusetts Institute Of Technology | Solution-phase affinity selection of inhibitors from combinatorial peptide libraries |
| AU2018385697B2 (en) | 2017-12-15 | 2023-11-09 | Dana-Farber Cancer Institute, Inc. | Stabilized peptide-mediated targeted protein degradation |
| US11505573B2 (en) | 2018-03-28 | 2022-11-22 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| US11819532B2 (en) | 2018-04-23 | 2023-11-21 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| US11091522B2 (en) | 2018-07-23 | 2021-08-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2020093055A2 (en) | 2018-11-02 | 2020-05-07 | Indi Molecular, Inc. | Peptide libraries with non-canonical amino acids |
| EP3938051A4 (en) * | 2019-03-15 | 2022-12-07 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN110721314B (zh) * | 2019-10-11 | 2022-11-29 | 江苏恒泰生物科技有限公司 | 一种抗肿瘤纳米药物及其制备方法 |
Family Cites Families (576)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1030010A (en) | 1907-05-27 | 1912-06-18 | Vermont Farm Machine Company | Cow-milking machine. |
| US1021347A (en) | 1908-03-07 | 1912-03-26 | Hans Windhoff | Hoisting-gear. |
| US1025306A (en) | 1909-06-24 | 1912-05-07 | Randolph R Rawle | Apparatus for aerial navigation. |
| US1005974A (en) | 1910-03-30 | 1911-10-17 | Samuel N House | Tenoning-machine. |
| US1024649A (en) | 1910-05-16 | 1912-04-30 | Peter Peel | Animal-releasing means. |
| US1020243A (en) | 1910-06-17 | 1912-03-12 | Gustav Adolf Wlost | Resonating device. |
| US1002361A (en) | 1910-10-13 | 1911-09-05 | Daniel N Baxter | Boiler-cleaner. |
| US1002242A (en) | 1910-12-27 | 1911-09-05 | Otto P W Ehrhardt | Cabbage-corer. |
| US1003004A (en) | 1911-01-16 | 1911-09-12 | Gustave J Martel | Repair-patch for pneumatic tires. |
| US1032811A (en) | 1911-02-01 | 1912-07-16 | James O Brookbank | Burner. |
| US1030135A (en) | 1911-05-13 | 1912-06-18 | Belisario Silfa | Spark-plug. |
| US1022738A (en) | 1911-10-24 | 1912-04-09 | Julius W Horvath | Spring-bed. |
| US1030869A (en) | 1911-11-06 | 1912-07-02 | Vittorio Buffulini | Wreck-raising appliance. |
| US1048711A (en) | 1912-02-23 | 1912-12-31 | John Uri Lloyd | Alkaloidal substance. |
| US1046497A (en) | 1912-03-15 | 1912-12-10 | Adam Sawicki | Nail holding and delivering apparatus. |
| US1047112A (en) | 1912-07-17 | 1912-12-10 | Ole P Noisom | Electric-circuit controller. |
| US4000259A (en) | 1975-06-16 | 1976-12-28 | American Home Products Corporation | Cyclic dodecapeptide analogs of somatostatin and intermediates |
| US4438270A (en) | 1977-07-11 | 1984-03-20 | Merrell Toraude Et Compagnie | α-Halomethyl derivatives of α-amino acids |
| US4191754A (en) | 1979-02-28 | 1980-03-04 | Merck & Co., Inc. | Bicyclic somatostatin analogs |
| US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| AU550730B2 (en) | 1982-03-09 | 1986-04-10 | Commonwealth Of Australia, The | Automated metal detection |
| US4728726A (en) | 1982-10-04 | 1988-03-01 | The Salk Institute For Biological Studies | GRF analogs IIIb |
| US4518586A (en) | 1983-01-13 | 1985-05-21 | The Salk Institute For Biological Studies | GRF Analogs III |
| US5416073A (en) | 1983-08-10 | 1995-05-16 | The Adminstrators Of The Tulane Educational Fund | Growth hormone-releasing peptides and method of treating animals, therewith |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US5036045A (en) | 1985-09-12 | 1991-07-30 | The University Of Virginia Alumni Patents Foundation | Method for increasing growth hormone secretion |
| US4730006A (en) | 1986-01-27 | 1988-03-08 | Merrell Dow Pharmaceuticals Inc. | Derivatives of 2,6-diamino-3-haloheptanedioic acid |
| US4880778A (en) | 1986-05-12 | 1989-11-14 | Eastman Kodak Company | Combinations having synergistic growth hormone releasing activity and methods for use thereof |
| HU906340D0 (en) | 1986-10-13 | 1991-04-29 | Sandoz Ag | Synthesis in solid phase for producing peptonic alcohols |
| CA1283827C (en) | 1986-12-18 | 1991-05-07 | Giorgio Cirelli | Appliance for injection of liquid formulations |
| GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US5112808A (en) | 1987-05-11 | 1992-05-12 | American Cyanamid Company | Alkylated hormone-releasing peptides and method of treatig mammals therewith |
| US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US5877277A (en) | 1987-09-24 | 1999-03-02 | Biomeasure, Inc. | Octapeptide bombesin analogs |
| US5453418A (en) | 1988-03-07 | 1995-09-26 | Eli Lilly And Company | Ractopamine and growth hormone combinations |
| US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| AU3439589A (en) | 1988-03-24 | 1989-10-16 | Terrapin Diagnostics, Inc. | Molecular sticks for controlling protein conformation |
| US5094951A (en) | 1988-06-21 | 1992-03-10 | Chiron Corporation | Production of glucose oxidase in recombinant systems |
| US5043322A (en) | 1988-07-22 | 1991-08-27 | The Salk Institute For Biological Studies | Cyclic GRF analogs |
| FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| US5384309A (en) | 1989-07-17 | 1995-01-24 | Genentech, Inc. | Cyclized peptides and their use as platelet aggregation inhibitors |
| US5120859A (en) | 1989-09-22 | 1992-06-09 | Genentech, Inc. | Chimeric amino acid analogues |
| US5650133A (en) | 1990-01-19 | 1997-07-22 | Nycomed Salutar | Macrocyclic polyaza dichelates linked through ring nitrogens via an amide or ester functionality |
| US5712418A (en) | 1989-10-23 | 1998-01-27 | Research Corporation Technologies, Inc. | Synthesis and use of amino acid fluorides as peptide coupling reagents |
| US5169932A (en) | 1989-10-30 | 1992-12-08 | The Salk Institute For Biological Studies | Gnrh analogs |
| US5352796A (en) | 1989-10-30 | 1994-10-04 | The Salk Institute For Biological Studies | Amino acids useful in making GnRH analogs |
| US5296468A (en) | 1989-10-30 | 1994-03-22 | The Salk Institute For Biological Studies | GnRH analogs |
| US5580957A (en) | 1989-10-30 | 1996-12-03 | The Salk Institute For Biological Studies | GnRH analogs |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5245009A (en) | 1990-03-23 | 1993-09-14 | The Salk Institute For Biological Studies | CRF antagonists |
| CA2047042A1 (en) | 1990-07-19 | 1992-01-20 | John Hannah | Cyclic hiv principal neutralizing determinant peptides |
| US5629020A (en) | 1994-04-22 | 1997-05-13 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
| US6344213B1 (en) | 1996-03-29 | 2002-02-05 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
| US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| AU8736691A (en) | 1990-10-11 | 1992-05-20 | Boehringer Ingelheim International Gmbh | Cyclopeptides, a method of preparing them, and their use as drugs |
| DE69118826T2 (de) | 1990-11-27 | 1996-11-14 | Fuji Photo Film Co Ltd | Propenamidderivate, deren Polymere, Copolymere und deren Verwendung |
| US5124454A (en) | 1990-11-30 | 1992-06-23 | Minnesota Mining And Manufacturing Company | Polycyclic diamines and method of preparation |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| AU1570292A (en) | 1991-02-07 | 1992-09-07 | Board Of Trustees Of The University Of Illinois, The | Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same |
| US5747469A (en) * | 1991-03-06 | 1998-05-05 | Board Of Regents, The University Of Texas System | Methods and compositions comprising DNA damaging agents and p53 |
| US5744450A (en) | 1991-03-14 | 1998-04-28 | The Salk Institute For Biological Studies | GnRH analogs |
| EP0542937A1 (en) | 1991-04-09 | 1993-05-26 | F. Hoffmann-La Roche Ag | Growth hormone releasing factor analogs |
| US5262519A (en) | 1991-05-15 | 1993-11-16 | The Salk Institute For Biological Studies | GRF analogs XI |
| US5364851A (en) | 1991-06-14 | 1994-11-15 | International Synthecon, Llc | Conformationally restricted biologically active peptides, methods for their production and uses thereof |
| CA2072249C (en) | 1991-06-28 | 2003-06-17 | Saiko Hosokawa | Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane |
| GB9114949D0 (en) | 1991-07-11 | 1991-08-28 | Smithkline Beecham Plc | Novel compounds |
| DK0528312T3 (da) | 1991-08-13 | 1997-12-29 | Takeda Chemical Industries Ltd | Cykliske peptider og anvendelse deraf |
| US7517644B1 (en) | 1991-08-23 | 2009-04-14 | Larry J. Smith | Method and compositions for cellular reprogramming |
| GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| IL103252A (en) | 1991-09-30 | 1997-03-18 | Du Pont Merck Pharma | CYCLIC COMPOUNDS USEFUL AS INHIBITORS OF PLATELET GLYCOPROTEIN IIb/IIIa AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| ES2133295T3 (es) | 1991-11-19 | 1999-09-16 | Takeda Chemical Industries Ltd | Peptidos ciclicos y su uso. |
| US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| EP1251135A3 (en) | 1992-04-03 | 2004-01-02 | California Institute Of Technology | High activity ruthenium or osmium metal carbene complexes for olefin metathesis reactions and synthesis thereof |
| US5411860A (en) | 1992-04-07 | 1995-05-02 | The Johns Hopkins University | Amplification of human MDM2 gene in human tumors |
| JPH08501280A (ja) | 1992-05-26 | 1996-02-13 | リュクスウニヴェルシテート レイデン | ヒトＴ細胞応答誘発組成物に用いるためのヒトｐ５３タンパク質のペプチドおよびヒトｐ５３タンパク質特異的細胞毒性Ｔリンパ球 |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| EP0651761B1 (en) | 1992-07-13 | 2002-10-09 | Bionebraska, Inc. | Method for modification of recombinant polypeptides |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| US5371070A (en) | 1992-11-09 | 1994-12-06 | The Salk Institute For Biological Studies | Bicyclic GnRH antagonists and a method for regulating the secretion of gonadotropins |
| WO1994018955A1 (en) | 1993-02-22 | 1994-09-01 | Alza Corporation | Compositions for oral delivery of active agents |
| WO1994022910A1 (en) | 1993-03-29 | 1994-10-13 | The Du Pont Merck Pharmaceutical Company | CYCLIC COMPOUNDS USEFUL AS INHIBITORS OF PLATELET GLYCOPROTEIN IIb/IIIa |
| US5643957A (en) | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO1994025482A1 (en) | 1993-04-23 | 1994-11-10 | Evans Herbert J | Polypeptides that include conformation-constraining groups which flank a protein-protein interaction site |
| US5446128A (en) | 1993-06-18 | 1995-08-29 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| KR100325972B1 (ko) | 1993-08-09 | 2002-07-27 | 바이오메져 인코퍼레이티드 | 치료성펩타이드유도체 |
| US5622852A (en) | 1994-10-31 | 1997-04-22 | Washington University | Bcl-x/Bcl-2 associated cell death regulator |
| US5536814A (en) | 1993-09-27 | 1996-07-16 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
| EP0734439A4 (en) | 1993-11-22 | 2000-07-12 | Onyx Pharma Inc | p53-binding polypeptides and polynucleotides that code for them |
| US6287787B1 (en) | 1993-11-24 | 2001-09-11 | Torrey Pines Institute For Molecular Studies | Dimeric oligopeptide mixture sets |
| WO1995022546A1 (en) | 1994-02-18 | 1995-08-24 | Cell Therapeutics, Inc. | Intracellular signalling mediators |
| WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| US5506207A (en) | 1994-03-18 | 1996-04-09 | The Salk Institute For Biological Studies | GNRH antagonists XIII |
| US5824483A (en) | 1994-05-18 | 1998-10-20 | Pence Inc. | Conformationally-restricted combinatiorial library composition and method |
| JP3166482B2 (ja) | 1994-06-07 | 2001-05-14 | 日産自動車株式会社 | 反射干渉作用を有する発色構造体 |
| US6407059B1 (en) | 1994-06-08 | 2002-06-18 | Peptor Limited | Conformationally constrained backbone cyclized peptide analogs |
| IL109943A (en) | 1994-06-08 | 2006-08-01 | Develogen Israel Ltd | Conformationally constrained backbone cyclized peptide analogs |
| US5807746A (en) | 1994-06-13 | 1998-09-15 | Vanderbilt University | Method for importing biologically active molecules into cells |
| US7553929B2 (en) | 1994-06-13 | 2009-06-30 | Vanderbilt University | Cell permeable peptides for inhibition of inflammatory reactions and methods of use |
| US5770377A (en) | 1994-07-20 | 1998-06-23 | University Of Dundee | Interruption of binding of MDM2 and P53 protein and therapeutic application thereof |
| US5702908A (en) | 1994-07-20 | 1997-12-30 | University Of Dundee | Interruption of binding of MDM2 and p53 protein and therapeutic application thereof |
| RU2161042C2 (ru) | 1994-09-19 | 2000-12-27 | Дж. Моро Рикардо | Обнаружение и лечение рака |
| CA2158782C (en) | 1994-09-23 | 2010-01-12 | Pierrette Gaudreau | Marker for growth hormone-releasing factor receptors |
| US5681928A (en) | 1994-12-16 | 1997-10-28 | The Salk Institute For Biological Studies | Betides and methods for screening peptides using same |
| AU719001B2 (en) | 1994-12-29 | 2000-05-04 | Massachusetts Institute Of Technology | Chimeric DNA-binding proteins |
| US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| US5792747A (en) | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| US6169073B1 (en) | 1995-02-16 | 2001-01-02 | Bayer Corporation | Peptides and peptidomimetics with structural similarity to human p53 that activate p53 function |
| EP0729972A1 (de) | 1995-02-28 | 1996-09-04 | F. Hoffmann-La Roche Ag | Tetrahydronaphthalin-Peptidderivate |
| US6514942B1 (en) | 1995-03-14 | 2003-02-04 | The Board Of Regents, The University Of Texas System | Methods and compositions for stimulating T-lymphocytes |
| US5675001A (en) | 1995-03-14 | 1997-10-07 | Hoffman/Barrett, L.L.C. | Heteroatom-functionalized porphyrazines and multimetallic complexes and polymers derived therefrom |
| US5700775A (en) | 1995-03-24 | 1997-12-23 | Gutniak; Mark K. | Method and treatment composition for decreasing patient time in catabolic state after traumatic injury |
| BR9604880A (pt) | 1995-03-31 | 1998-05-19 | Emisphere Tech Inc | Composto composição forma de unidade de dosagem métodos para administração de um agente biologicamente ativo para preparar uma composição para administração de um agente ativo e para preparar um composto e composição farmacológica |
| US6090958A (en) | 1995-03-31 | 2000-07-18 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US6054556A (en) | 1995-04-10 | 2000-04-25 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Melanocortin receptor antagonists and agonists |
| US5731408A (en) | 1995-04-10 | 1998-03-24 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Peptides having potent antagonist and agonist bioactivities at melanocortin receptors |
| CA2218173A1 (en) | 1995-04-14 | 1996-10-17 | The Administrators Of The Tulane Educational Fund | Analogs of growth hormone-releasing factor |
| US5672584A (en) | 1995-04-25 | 1997-09-30 | The University Of Kansas | Cyclic prodrugs of peptides and peptide nucleic acids having improved metabolic stability and cell membrane permeability |
| US6184344B1 (en) | 1995-05-04 | 2001-02-06 | The Scripps Research Institute | Synthesis of proteins by native chemical ligation |
| DE69521815T2 (de) | 1995-05-04 | 2002-04-04 | The Scripps Research Institute, La Jolla | Proteinsynthese mittels nativer chemischer ligation (07.01.97) |
| US6020311A (en) | 1995-05-26 | 2000-02-01 | Theratechnologies, Inc. | GRF analogs with increased biological potency |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| PT828758E (pt) | 1995-05-26 | 2002-02-28 | Theratechnologies Inc | Analogos quimericos de corpo gordo-pro-grf com potencia biologica aumentada |
| US6458764B1 (en) | 1995-05-26 | 2002-10-01 | Theratechnologies Inc. | GRF analogs with increased biological potency |
| US5817789A (en) | 1995-06-06 | 1998-10-06 | Transkaryotic Therapies, Inc. | Chimeric proteins for use in transport of a selected substance into cells |
| US6051554A (en) | 1995-06-07 | 2000-04-18 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
| US6413994B1 (en) | 1999-02-22 | 2002-07-02 | The Salk Institute For Biological Studies | Modulators of peroxisome proliferator activated receptor-gamma, and methods for the use thereof |
| US5811515A (en) | 1995-06-12 | 1998-09-22 | California Institute Of Technology | Synthesis of conformationally restricted amino acids, peptides, and peptidomimetics by catalytic ring closing metathesis |
| FR2738151B1 (fr) | 1995-09-04 | 1997-09-26 | Rhone Poulenc Rorer Sa | Antagonistes de l'activite oncogenique de la proteine mdm2, et leur utilisation dans le traitement des cancers |
| EP0766966A3 (en) | 1995-09-08 | 2001-02-28 | Eli Lilly And Company | Method of treating insulin resistance |
| US5750499A (en) | 1995-10-18 | 1998-05-12 | The Salk Institute For Biological Studies | Receptor-selective somatostatin analogs |
| GB9521544D0 (en) | 1995-10-20 | 1995-12-20 | Univ Dundee | Activation of P53 protein and therapeutic applications thereof |
| US5840833A (en) | 1995-10-27 | 1998-11-24 | Molecumetics, Ltd | Alpha-helix mimetics and methods relating thereto |
| US6123964A (en) | 1995-10-27 | 2000-09-26 | Merck & Co., Inc. | Wet granulation formulation of a growth hormone secretagogue |
| EP0869974B1 (en) | 1995-12-22 | 2009-03-04 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| US5807983A (en) | 1995-12-28 | 1998-09-15 | The Salk Institute For Biological Studies | GNRH antagonist betides |
| US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| EP0880357A4 (en) | 1996-01-17 | 1999-05-12 | California Inst Of Techn | SYNTHESIS OF CONFORMATORICALLY RESTRICTED AMINO ACIDS, PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS BY CATALYTIC RINGCLOSE METATHESIS |
| US5849954A (en) | 1996-01-18 | 1998-12-15 | Research Corporation Technologies, Inc. | Method of peptide synthesis |
| US5849691A (en) | 1996-02-20 | 1998-12-15 | The United States Of America As Represented By The Department Of Health And Human Services | Peptidomimetic inhibitors of cathepsin D and plasmepsins I and II |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| JP3792777B2 (ja) | 1996-05-10 | 2006-07-05 | 株式会社カネカ | １−アルコキシカルボニル−３−フェニルプロピル誘導体の製造方法 |
| US6071926A (en) | 1996-05-22 | 2000-06-06 | Arch Development Corporation | Sleep quality improvement using a growth hormone secretagogue |
| US5817752A (en) | 1996-06-06 | 1998-10-06 | La Jolla Pharmaceutical Company | Cyclic polypeptides comprising a thioether linkage and methods for their preparation |
| US5817627A (en) | 1996-06-14 | 1998-10-06 | Theratechnologies Inc. | Long-acting galenical formulation for GRF peptides |
| ES2136458T3 (es) | 1996-06-14 | 1999-11-16 | Takeda Chemical Industries Ltd | Metodo para separar la metionina n-terminal. |
| US5663316A (en) | 1996-06-18 | 1997-09-02 | Clontech Laboratories, Inc. | BBC6 gene for regulation of cell death |
| US7083983B2 (en) | 1996-07-05 | 2006-08-01 | Cancer Research Campaign Technology Limited | Inhibitors of the interaction between P53 and MDM2 |
| DE69738754D1 (de) | 1996-07-05 | 2008-07-17 | Cancer Rec Tech Ltd | Hemmer der interaktion zwischen p53 und mdm2 |
| ATE304528T1 (de) | 1996-07-22 | 2005-09-15 | Novo Nordisk As | Verbindungen mit wachstumshormon-freisetzenden eigenschaften |
| US5955593A (en) | 1996-09-09 | 1999-09-21 | Washington University | BH3 interacting domain death agonist |
| US20020064546A1 (en) | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
| US5965703A (en) | 1996-09-20 | 1999-10-12 | Idun Pharmaceuticals | Human bad polypeptides, encoding nucleic acids and methods of use |
| GB9619757D0 (en) | 1996-09-21 | 1996-11-06 | Knoll Ag | Chemical process |
| US5856445A (en) | 1996-10-18 | 1999-01-05 | Washington University | Serine substituted mutants of BCL-XL /BCL-2 associated cell death regulator |
| JP4024309B2 (ja) | 1996-10-22 | 2007-12-19 | 第一三共株式会社 | 新規な感染症治療薬 |
| US6271198B1 (en) | 1996-11-06 | 2001-08-07 | Genentech, Inc. | Constrained helical peptides and methods of making same |
| WO1998022122A1 (en) | 1996-11-21 | 1998-05-28 | Promega Corporation | Alkyl peptide amides and applications |
| US6060513A (en) | 1997-02-07 | 2000-05-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| CZ290347B6 (cs) | 1997-02-07 | 2002-07-17 | Ústav organické chemie a biochemie AV ČR | Cyklopeptidy stimulující uvolňování růstového hormonu a způsob jejich přípravy |
| US6313088B1 (en) | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
| EA199900752A1 (ru) | 1997-02-20 | 2000-06-26 | Йеда Рисерч Энд Дивелопмент Ко. Лтд. | Противопатогенные синтетические пептиды и композиции, их включающие |
| US6849428B1 (en) | 1997-03-05 | 2005-02-01 | New England Biolabs, Inc. | Intein-mediated protein ligation of expressed proteins |
| US6635740B1 (en) | 1997-03-27 | 2003-10-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Ligand/lytic peptide compositions and methods of use |
| EP1015479A4 (en) | 1997-04-11 | 2002-07-24 | Lilly Co Eli | COMBINATIVE SUBSTANCE LIBRARIES OF PEPTIDOMIMETIC MACROCYCLES AND THE RELATED METHODS |
| GB9708092D0 (en) | 1997-04-22 | 1997-06-11 | Univ Dundee | Materials and methods relating to inhibiting the interaction of p53 and mdm2 |
| US6329368B1 (en) | 1997-05-09 | 2001-12-11 | The Regents Of The University Of California | Endocrine modulation with positive modulators of AMPA type glutamate receptors |
| US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| US6127341A (en) | 1997-06-20 | 2000-10-03 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| US6248358B1 (en) | 1998-08-25 | 2001-06-19 | Columbia Laboratories, Inc. | Bioadhesive progressive hydration tablets and methods of making and using the same |
| EP1015578A4 (en) | 1997-09-17 | 2004-12-01 | Walker And Eliza Hall Inst Of | THERAPEUTIC MOLECULES |
| CA2305809A1 (en) | 1997-09-26 | 1999-04-08 | University Technologies International, Inc. | Use of the tumour suppressor gene p33ing1 for modulation of p53 activity and in tumour diagnosis |
| US6165732A (en) | 1997-10-14 | 2000-12-26 | Washington University | Method for identifying apoptosis modulating compounds |
| US6875594B2 (en) | 1997-11-13 | 2005-04-05 | The Rockefeller University | Methods of ligating expressed proteins |
| US6177076B1 (en) * | 1997-12-09 | 2001-01-23 | Thomas Jefferson University | Method of treating bladder cancer with wild type vaccinia virus |
| EP1053019B1 (en) | 1998-01-07 | 2003-12-03 | Debio Recherche Pharmaceutique S.A. | Degradable heterobifunctional poly(ethylene glycol) acrylates and gels and conjugates derived therefrom |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| US6030997A (en) | 1998-01-21 | 2000-02-29 | Eilat; Eran | Acid labile prodrugs |
| WO1999038535A1 (en) | 1998-01-29 | 1999-08-05 | Kinerton Limited | Process for making absorbable microparticles |
| JP3842042B2 (ja) | 1998-01-29 | 2006-11-08 | ポリ−メド・インコーポレーテッド | 吸収可能なマイクロ粒子 |
| IL138214A0 (en) | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| AU767185B2 (en) | 1998-03-23 | 2003-11-06 | President And Fellows Of Harvard College | Synthesis of compounds and libraries of compounds |
| CA2325572A1 (en) | 1998-04-15 | 1999-10-21 | Aventis Pharmaceuticals Products Inc. | Process for the preparation of resin-bound cyclic peptides |
| US6190699B1 (en) | 1998-05-08 | 2001-02-20 | Nzl Corporation | Method of incorporating proteins or peptides into a matrix and administration thereof through mucosa |
| US6288234B1 (en) | 1998-06-08 | 2001-09-11 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
| US6326354B1 (en) | 1998-08-19 | 2001-12-04 | Washington University | Modulation of apoptosis with bid |
| US7173005B2 (en) | 1998-09-02 | 2007-02-06 | Antyra Inc. | Insulin and IGF-1 receptor agonists and antagonists |
| US6194402B1 (en) | 1998-09-02 | 2001-02-27 | Merck & Co., Inc. | Enhancement of return to independent living status with a growth hormone secretagogue |
| US6572856B1 (en) | 1998-09-10 | 2003-06-03 | The University Of Virginia Patent Foundation | Methods for the prevention and treatment of cancer using anti-C3b(i) antibodies |
| US6696063B1 (en) | 1998-12-30 | 2004-02-24 | Applied Research Systems Ars Holding N.V. | Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy |
| DE60037394T2 (de) | 1999-01-29 | 2009-01-02 | The Board Of Trustees For The University Of Illinois, Urbana | VERWENDUNG VON p53 INHIBITOREN ZUR BEHANDLUNG VON NEBENERSCHEINUNGEN BEI DER KREBSTHERAPIE |
| US6372490B1 (en) | 1999-02-23 | 2002-04-16 | Curagen Corporation | Nucleic acid encoding the MDM interacting protein |
| CA2363077A1 (en) | 1999-03-01 | 2000-09-08 | Variagenics, Inc. | Methods for targeting rna molecules |
| WO2000058361A1 (en) | 1999-03-29 | 2000-10-05 | The Procter & Gamble Company | Melanocortin receptor ligands |
| US6444425B1 (en) | 1999-04-02 | 2002-09-03 | Corixa Corporation | Compounds for therapy and diagnosis of lung cancer and methods for their use |
| US6713280B1 (en) | 1999-04-07 | 2004-03-30 | Thomas Jefferson University | Enhancement of peptide cellular uptake |
| US6346264B1 (en) | 1999-04-27 | 2002-02-12 | International Health Products And Services Ltd. | Supplement for restoring growth hormone levels |
| EP1623994A3 (en) | 1999-05-17 | 2008-07-16 | ConjuChem Biotechnologies Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US20090175821A1 (en) | 1999-05-17 | 2009-07-09 | Bridon Dominique P | Modified therapeutic peptides with extended half-lives in vivo |
| US7192713B1 (en) | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| WO2000071096A2 (en) | 1999-05-24 | 2000-11-30 | Introgen Therapeutics, Inc. | Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases |
| ATE309358T1 (de) | 1999-07-26 | 2005-11-15 | Baylor College Medicine | Superaktive, wachstumshormone freisetzende hormonanaloge vom schwein |
| US6461634B1 (en) | 1999-08-20 | 2002-10-08 | Edward Marshall | Food-based delivery of HGH-stimulating and other nutritional supplements |
| US20080032931A1 (en) | 1999-08-25 | 2008-02-07 | Steward Lance E | Activatable clostridial toxins |
| US20020016298A1 (en) | 1999-09-01 | 2002-02-07 | Hay Bruce A. | Somatostatin antagonists and agonists that act at the sst subtype 2 receptor |
| US6696418B1 (en) | 1999-09-01 | 2004-02-24 | Pfizer Inc. | Somatostatin antagonists and agonists that act at the SST subtype 2 receptor |
| US20030181367A1 (en) | 1999-09-27 | 2003-09-25 | O'mahony Daniel | Conjugates of membrane translocating agents and pharmaceutically active agents |
| AU1925701A (en) | 1999-11-22 | 2001-06-04 | Zymogenetics Inc. | Method of forming a peptide-receptor complex with zsig33 |
| US6831155B2 (en) | 1999-12-08 | 2004-12-14 | President And Fellows Of Harvard College | Inhibition of p53 degradation |
| US6348558B1 (en) | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6579967B1 (en) | 1999-12-14 | 2003-06-17 | The Salk Institute For Biological Studies | Receptor-selective somatostatin analogs |
| US20030087263A1 (en) | 1999-12-16 | 2003-05-08 | Renu Wadhwa | Method of screening remedy for cancer with the use of interaction domain of p53 and mortalin |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| US20010020012A1 (en) | 2000-02-01 | 2001-09-06 | Andersen Maibritt Bansholm | Use of compounds for the regulation of food intake |
| DE10009341A1 (de) | 2000-02-22 | 2001-09-06 | Florian Kern | Verfahren zur antigen-spezifischen Stimulation von T-Lymphozyten |
| US6495674B1 (en) | 2000-02-25 | 2002-12-17 | The Salk Institute For Biological Studies | Evectins and their use |
| US20020002198A1 (en) | 2000-04-17 | 2002-01-03 | Parr Tyler B. | Chemical synergy to elevate growth hormone release in vertebrates |
| US6495589B2 (en) | 2000-04-28 | 2002-12-17 | Pfizer Inc. | Somatostatin antagonists and agonists that act at the SST subtype 2 receptor |
| US6897286B2 (en) | 2000-05-11 | 2005-05-24 | Zymogenetics, Inc. | Zsig33-like peptides |
| US20020061838A1 (en) | 2000-05-17 | 2002-05-23 | Barton Holmquist | Peptide pharmaceutical formulations |
| ES2333097T3 (es) | 2000-05-31 | 2010-02-17 | Raqualia Pharma Inc | Uso de secretagogos de la hormona de crecimiento para estimular la motilidad gastrointestinal. |
| IL143690A0 (en) | 2000-06-19 | 2002-04-21 | Pfizer Prod Inc | The use of growth hormone secretagogues to treat systemic lupus erythematosus and inflammatory bowel disease |
| IL143942A0 (en) | 2000-06-29 | 2002-04-21 | Pfizer Prod Inc | Use of growth hormone secretagogues for treatment of physical performance decline |
| US7166712B2 (en) | 2000-07-12 | 2007-01-23 | Philadelphia, Health And Education Corporation | Mammalian MDM2 binding proteins and uses thereof |
| IL144468A0 (en) | 2000-07-27 | 2002-05-23 | Pfizer Prod Inc | Use of growth hormone secretagogues for improvement of functional health status |
| US7049290B2 (en) | 2000-07-28 | 2006-05-23 | Universität Zürich | Essential downstream component of the wingless signaling pathway and therapeutic and diagnostic applications based thereon |
| US20030204063A1 (en) | 2000-08-02 | 2003-10-30 | Denis Gravel | Modified biological peptides with increased potency |
| US20040228866A1 (en) | 2000-08-04 | 2004-11-18 | Ludwig Institute For Cancer Research | Suppressor genes |
| AU2001284942A1 (en) | 2000-08-16 | 2002-02-25 | Georgetown University Medical Center | Small molecule inhibitors targeted at bcl-2 |
| IL145106A0 (en) | 2000-08-30 | 2002-06-30 | Pfizer Prod Inc | Intermittent administration of a geowth hormone secretagogue |
| EP1313473A2 (en) | 2000-08-30 | 2003-05-28 | Pfizer Products Inc. | Sustained release formulations for growth hormone secretagogues |
| AU2001273385B2 (en) | 2000-09-08 | 2005-04-07 | Gryphon Therapeutics, Inc. | Polymer-modified synthetic proteins |
| US6720330B2 (en) | 2000-11-17 | 2004-04-13 | Pfizer Inc. | Somatostatin antagonists and agonists that act at the SST subtype 2 receptor |
| US20030074679A1 (en) | 2000-12-12 | 2003-04-17 | Schwartz Robert J. | Administration of nucleic acid sequence to female animal to enhance growth in offspring |
| WO2002064790A2 (en) | 2000-12-19 | 2002-08-22 | The Johns Hopkins University | Jfy1 protein induces rapid apoptosis |
| US20020091090A1 (en) | 2000-12-28 | 2002-07-11 | Cole Bridget M. | Somatostatin antagonists and agonists |
| CU23157A1 (es) | 2001-01-03 | 2006-07-18 | Ct Ingenieria Genetica Biotech | COMPOSICION FARMACéUTICA PARA EL TRATAMIENTO DEL DANO TISULAR DEBIDO A FALTA DE IRRIGACION SANGUINEA ARTERIAL |
| EP1355941A2 (en) | 2001-02-02 | 2003-10-29 | ConjuChem, Inc. | Long lasting growth hormone releasing factor derivatives |
| JP4310106B2 (ja) | 2001-02-23 | 2009-08-05 | ポリファー リミテッド | 抗菌活性を有するテンプレート結合ペプチド擬似体 |
| GB0104588D0 (en) | 2001-02-24 | 2001-04-11 | Univ Dundee | Novel p-53 inducible protein |
| DE10109813A1 (de) | 2001-03-01 | 2002-09-12 | Thomas Stanislawski | Tumor-Peptidantigen aus humanem mdm2 Proto-Onkogen |
| AU2002252246A1 (en) | 2001-03-09 | 2002-09-24 | University Of Louisville | Helicomimetics and stabilized lxxll peptidomimetics |
| US7019109B2 (en) | 2001-03-16 | 2006-03-28 | The Salk Institute For Bilogical Studies | SSTR1-selective analogs |
| KR20030088494A (ko) | 2001-04-09 | 2003-11-19 | 더 어드미니스트레이터즈 오브 더 튜래인 어듀케이셔널 훤드 | 소마토스타틴 작용제 |
| US6368617B1 (en) | 2001-05-15 | 2002-04-09 | Reliv' International, Inc. | Dietary supplement |
| AU2002312230A1 (en) | 2001-06-05 | 2002-12-16 | Elan Pharma International Limited | System and method for milling materials |
| WO2003004068A1 (en) | 2001-07-06 | 2003-01-16 | Auckland Uniservices Limited | Hypertension treatment |
| WO2003014056A1 (fr) | 2001-08-08 | 2003-02-20 | Kaneka Corporation | Procede de production d'un acide carboxylique 2-substitue optiquement actif |
| EP1578901A4 (en) | 2001-09-07 | 2006-03-29 | Baylor College Medicine | LINEAR DNA FRAGMENTS FOR GENE EXPRESSION |
| US20040106548A1 (en) | 2001-09-07 | 2004-06-03 | Schmidt Michelle A | Conformationally constrained labeled peptides for imaging and therapy |
| US20020045192A1 (en) | 2001-09-19 | 2002-04-18 | St. Jude Children's Research Hospital | Arf and HDM2 interaction domains and methods of use thereof |
| EP1312363A1 (en) | 2001-09-28 | 2003-05-21 | Pfizer Products Inc. | Methods of treatment and kits comprising a growth hormone secretagogue |
| US20030083241A1 (en) | 2001-11-01 | 2003-05-01 | Young Charles W. | Use of somatostatin receptor agonists in the treatment of human disorders of sleep hypoxia and oxygen deprivation |
| CN101157924A (zh) | 2001-12-11 | 2008-04-09 | 人体基因组科学有限公司 | 嗜中性白细胞因子α |
| WO2003051389A2 (en) | 2001-12-18 | 2003-06-26 | Theratechnologies Inc. | Pharmaceutical compositions comprising unacylated ghrelin and therapeutical uses thereof |
| EP1321474A1 (en) | 2001-12-18 | 2003-06-25 | Universite De Geneve | A method for inducing apoptosis |
| US20050043231A1 (en) | 2001-12-24 | 2005-02-24 | Cutfield Wayne Stephen | Therapy for growth hormone induced insulin resistance in juveniles with growth disorders |
| WO2003057158A2 (en) | 2001-12-31 | 2003-07-17 | Dana-Farber Cancer Institute, Inc. | Method of treating apoptosis and compositions thereof |
| IL162604A0 (en) | 2002-01-03 | 2005-11-20 | Yissum Res Dev Co | Conformationally constrained c-backbone cyclic peptides |
| AU2003215082B2 (en) | 2002-02-07 | 2011-11-10 | Baylor College Of Medicine | Modified pituitary gland development in offspring from expectant mother animals treated with growth hormone releasing hormone therapy |
| AU2003219787A1 (en) | 2002-02-14 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Formulation strategies in stabilizing peptides in organic solvents and in dried states |
| AU2003211093A1 (en) | 2002-02-15 | 2003-09-09 | The Regents Of The University Of Michigan | Inhibitors of rgs proteins |
| US20030166138A1 (en) | 2002-02-21 | 2003-09-04 | Todd Kinsella | Cyclic peptides and analogs useful to treat allergies |
| EP1490696A2 (en) | 2002-03-26 | 2004-12-29 | Bayer Aktiengesellschaft | Diagnostics and therapeutics for diseases associated with growth hormone secretagogue receptor (ghs) |
| US7498134B2 (en) | 2002-03-30 | 2009-03-03 | The Trustees Of Columbia University In The City Of New York | HAUSP-Mdm2 interaction and uses thereof |
| US7524630B2 (en) | 2002-04-22 | 2009-04-28 | University Of Florida Research Foundation, Inc. | Functionalized nanoparticles and methods of use |
| AU2003235504A1 (en) | 2002-05-13 | 2003-11-11 | 3-Dimensional Pharmaceuticals, Inc. | Method for cytoprotection through mdm2 and hdm2 inhibition |
| WO2003102538A2 (en) | 2002-05-30 | 2003-12-11 | European Molecular Biology Laboratory | Combinatorial chemical library ii |
| ES2346646T5 (es) | 2002-05-30 | 2018-02-15 | The Scripps Research Institute | Ligación catalizada con cobre de azidas y acetilenos |
| US7208154B2 (en) | 2002-06-03 | 2007-04-24 | Regents Of The University Of Michigan | Methods and compositions for the treatment of MHC-associated conditions |
| SE0201863D0 (en) | 2002-06-18 | 2002-06-18 | Cepep Ab | Cell penetrating peptides |
| AU2003253883A1 (en) | 2002-07-15 | 2004-02-02 | The Johns Hopkins University | Neuronal and optic nerve gene expression patterns |
| WO2004009614A2 (en) | 2002-07-24 | 2004-01-29 | The Salk Institute For Biological Studies | Receptor (sstr4)- selective somatostatin analogs |
| EP1541692A1 (en) | 2002-09-06 | 2005-06-15 | Kaneka Corporation | PROCESS FOR PRODUCING L-a-METHYLCYSTEINE DERIVATIVE |
| JP2006516383A (ja) | 2002-09-09 | 2006-07-06 | デイナ−ファーバー キャンサー インスティチュート，インコーポレイテッド | Ｂｈ３ペプチドおよびその使用方法 |
| WO2004027064A2 (en) | 2002-09-18 | 2004-04-01 | Centre Hospitalier De L'universite De Montreal (Chum) | Ghrh analogues |
| WO2004026896A2 (en) | 2002-09-23 | 2004-04-01 | Medivir Ab | Hcv ns-3 serine protease inhibitors |
| CA2500665A1 (en) | 2002-10-07 | 2004-04-22 | Zymogenetics, Inc. | Methods of regulating body weight |
| ATE425183T1 (de) | 2002-10-07 | 2009-03-15 | Ludwig Inst For Cancer Res Ltd | P53-bindendes polypeptid |
| EP1407779A1 (en) | 2002-10-10 | 2004-04-14 | Gastrotech A/S | Use of ghrelin for treating low body weight and body fat in gastrectomized individuals |
| CN101003459B (zh) | 2002-10-24 | 2011-08-10 | 陶氏环球技术有限责任公司 | 烯烃易位产物混合物的稳定 |
| SI1562941T1 (sl) | 2002-11-07 | 2010-05-31 | Kosan Biosciences Inc | Trans dehidroepotilon c in d njihovi analogi in postopek za izdelavo le teh |
| CA2503117C (en) | 2002-11-08 | 2010-12-21 | F. Hoffmann-La Roche Ag | Substituted 4-alkoxyoxazol derivatives as ppar agonists |
| US20050227932A1 (en) | 2002-11-13 | 2005-10-13 | Tianbao Lu | Combinational therapy involving a small molecule inhibitor of the MDM2: p53 interaction |
| US7166575B2 (en) | 2002-12-17 | 2007-01-23 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity |
| AU2003291967A1 (en) | 2002-12-20 | 2004-07-14 | 7Tm Pharma A/S | Ghrelin receptor inverse agonist for regulation of feeding behaviours |
| US20070032417A1 (en) | 2002-12-24 | 2007-02-08 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| US20040231909A1 (en) | 2003-01-15 | 2004-11-25 | Tai-Yang Luh | Motorized vehicle having forward and backward differential structure |
| CA2513743C (en) | 2003-01-28 | 2013-06-25 | Advisys, Inc. | Reducing culling in herd animals growth hormone releasing hormone (ghrh) |
| WO2004067548A2 (en) | 2003-01-31 | 2004-08-12 | Theratechnologies Inc. | Chemically modified metabolites of regulatory peptides and methods of producing and using same |
| US7638138B2 (en) | 2003-02-21 | 2009-12-29 | Translational Research, Ltd. | Compositions for nasal administration of pharmaceuticals |
| CA2517285A1 (en) | 2003-02-26 | 2004-09-10 | Japan Science And Technology Agency | Transcriptional factor inducing apoptosis in cancer cell |
| EP1452868A2 (en) | 2003-02-27 | 2004-09-01 | Pepscan Systems B.V. | Method for selecting a candidate drug compound |
| US20070060512A1 (en) | 2003-03-04 | 2007-03-15 | Homayoun Sadeghi | Dipeptidyl-peptidase protected protein |
| WO2004084943A1 (en) | 2003-03-19 | 2004-10-07 | Beth Israel Deaconess Medical Center, Inc | Use of antagonists of ghrelin or ghrelin receptor to treat intestinal inflammation |
| US7632920B2 (en) | 2003-04-10 | 2009-12-15 | Schering Corporation | Soluble, stable form of HDM2, crystalline forms thereof and methods of use thereof |
| WO2004103390A2 (en) | 2003-05-15 | 2004-12-02 | Trustees Of Tufts College | Stable analogs of peptide and polypeptide therapeutics |
| EP1628676A1 (en) | 2003-05-29 | 2006-03-01 | Theratechnologies Inc. | Grf analog compositions and their use |
| AU2003902743A0 (en) | 2003-06-02 | 2003-06-19 | Promics Pty Limited | Process for the preparation of cyclic peptides |
| JP2007500243A (ja) | 2003-06-09 | 2007-01-11 | ナステック・ファーマシューティカル・カンパニー・インコーポレーテッド | 成長ホルモンの増進された経粘膜送達のための組成物および方法 |
| US20090198050A1 (en) | 2003-06-18 | 2009-08-06 | Tranzyme Pharma Inc. | Macrocyclic Modulators of the Ghrelin Receptor |
| CA2528375C (en) | 2003-06-18 | 2013-11-19 | Tranzyme Pharma, Inc. | Macrocyclic antagonists of the motilin receptor |
| USRE42013E1 (en) | 2003-06-18 | 2010-12-28 | Tranzyme Pharma Inc. | Macrocyclic modulators of the ghrelin receptor |
| USRE42624E1 (en) | 2003-06-18 | 2011-08-16 | Tranzyme Pharma Inc. | Methods of using macrocyclic modulators of the ghrelin receptor |
| US7476653B2 (en) | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
| US7491695B2 (en) | 2003-06-18 | 2009-02-17 | Tranzyme Pharma Inc. | Methods of using macrocyclic modulators of the ghrelin receptor |
| WO2005000876A2 (en) | 2003-06-27 | 2005-01-06 | Proteologics, Inc. | Ring finger family proteins and uses related thereto |
| WO2005007675A2 (en) | 2003-07-09 | 2005-01-27 | The Scripps Research Institute | TRIAZOLE ϵ-AMINO ACIDS |
| US20070185031A1 (en) | 2003-07-14 | 2007-08-09 | Northwestern University | Reducing polyglutamine-based aggregation |
| GB0317815D0 (en) | 2003-07-30 | 2003-09-03 | Amersham Health As | Imaging agents |
| CA2536112A1 (en) | 2003-08-20 | 2005-03-03 | Northern Sydney And Central Coast Area Health Service | Methods for enhancing embryo viability |
| WO2005018682A2 (en) | 2003-08-20 | 2005-03-03 | The Regents Of The University Of California | Somatostatin analogs with inhibitory activity to growth hormone release |
| WO2005027913A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue |
| CA2541090C (en) | 2003-10-03 | 2013-04-16 | Veijlen N.V. | Use of indole acetic acid or derivatives thereof to increase igf-1 serum levels |
| DE602004014170D1 (de) | 2003-10-03 | 2008-07-10 | Merck & Co Inc | Benzylether- und benzylamino-beta-sekretase-hemmer zur behandlung von alzheimer-krankheit |
| GB0323728D0 (en) | 2003-10-10 | 2003-11-12 | Royal College Of Surgeons Ie | Peptidomimetics and uses thereof |
| US20070207947A1 (en) | 2003-10-16 | 2007-09-06 | Aplagen Gmbh | Stabilized Peptides |
| US20070274915A1 (en) | 2003-10-17 | 2007-11-29 | Anjana Rao | Modulation Of Anergy And Methods For isolating Anergy-Modulating Compounds |
| EP1675610A4 (en) | 2003-10-20 | 2010-04-28 | Theratechnologies Inc | USE OF GROWTH HORMONE RELEASE FACTOR ANALOGUE IN THE TREATMENT OF PATIENTS WITH EXCEPTION |
| US7273927B2 (en) | 2003-11-03 | 2007-09-25 | University Of Massachusetts | Mdm2 splice variants |
| WO2005044839A2 (en) | 2003-11-05 | 2005-05-19 | Dana-Farber Cancer Institute, Inc. | Stabilized alpha helical peptides and uses thereof |
| US20050147581A1 (en) | 2003-11-19 | 2005-07-07 | The Board Of Trustees Of The University Of Illinois | Macromolecular drug complexes having improved stability and therapeutic use of the same |
| WO2005074521A2 (en) | 2004-01-30 | 2005-08-18 | The Trustees Of Columbia University In The City Of New York | C-TERMINAL p53 PALINDROMIC PEPTIDE THAT INDUCES APOPTOSIS OF CELLS WITH ABERRANT p53 AND USES THEREOF |
| US20070161551A1 (en) | 2004-02-10 | 2007-07-12 | De Luca Giampiero | Methods and compositions for the treatment of lipodystrophy |
| GB0404731D0 (en) | 2004-03-03 | 2004-04-07 | Indp Administrative Inst Nims | Method and products for the selective degradation of proteins |
| US20050203009A1 (en) | 2004-03-12 | 2005-09-15 | Bayer Pharmaceuticals Corporation | VPAC1 selective antagonists and their pharmacological methods of use |
| EP1737884B1 (en) | 2004-03-19 | 2016-10-19 | The University Of Queensland | Alpha helical mimics, their uses and methods for their production |
| KR20070010151A (ko) | 2004-03-30 | 2007-01-22 | 사파이어 세라퓨틱스, 인크. | 성장 호르몬 분비촉진제를 이용하여 ｃ-반응성 단백질을감소시키는 방법 |
| US20080171700A1 (en) | 2004-04-07 | 2008-07-17 | Gastrotech Pharma A/S | Use Of Secretagogue For The Teatment Of Ghrelin Deficiency |
| US7034050B2 (en) | 2004-04-28 | 2006-04-25 | Romano Deghenghi | Pseudopeptides growth hormone secretagogues |
| CN1953965B (zh) | 2004-05-18 | 2012-07-04 | 霍夫曼-拉罗奇有限公司 | 新型顺式咪唑啉类化合物 |
| US7202332B2 (en) | 2004-05-27 | 2007-04-10 | New York University | Methods for preparing internally constrained peptides and peptidomimetics |
| EP1602663A1 (en) | 2004-06-04 | 2005-12-07 | Chiralix B.V. | Triazole-linked glycoamino acids and glycopeptides |
| CN100335467C (zh) | 2004-06-04 | 2007-09-05 | 中国科学院上海有机化学研究所 | 一锅法区域选择性合成5－碘代－1，4－二取代－1，2，3－三氮唑化合物 |
| US7501397B2 (en) | 2004-06-04 | 2009-03-10 | The Brigham And Women's Hospital, Inc. | Helical peptidomimetics with enhanced activity |
| US7893278B2 (en) | 2004-06-17 | 2011-02-22 | Hoffman-La Roche Inc. | CIS-imidazolines |
| CA2568952C (en) | 2004-06-18 | 2019-05-21 | Ambrx, Inc. | Novel antigen-binding polypeptides and their uses |
| WO2006010118A2 (en) | 2004-07-09 | 2006-01-26 | The Regents Of The University Of Michigan | Conformationally constrained smac mimetics and the uses thereof |
| US8039456B2 (en) | 2004-08-12 | 2011-10-18 | Helsinn Therapeutics (U.S.), Inc. | Method of stimulating the motility of the gastrointestinal system using ipamorelin |
| AU2005272598B2 (en) | 2004-08-12 | 2011-11-17 | Helsinn Therapeutics (U.S.), Inc. | Method of stimulating the motility of the gastrointestinal system using growth hormone secretagogues |
| US20080261873A1 (en) | 2004-08-18 | 2008-10-23 | Elixir Pharmaceuticals, Inc. | Growth-Hormone Secretagogues |
| US7151084B2 (en) | 2004-12-27 | 2006-12-19 | Miller Landon C G | Compound and method of treating neurogenic conditions using non-steroidal anti-inflammatory drug complexes |
| US7402652B2 (en) | 2004-09-14 | 2008-07-22 | Miller Landon C G | Baclofen conjugate and a pharmaceutical composition for treatment of neuronal disorders |
| US7157421B2 (en) | 2004-12-27 | 2007-01-02 | Miller Landon C G | Piracetam and piracetam analog conjugate and a pharmaceutical composition for treatment of neuronal disorders |
| US7074775B2 (en) | 2004-09-14 | 2006-07-11 | Miller Landon C G | Aminobutyramide conjugate and a pharmaceutical composition for treatment of neuronal disorders |
| US9598470B2 (en) | 2004-10-07 | 2017-03-21 | Craig W. Beattie | Compositions and methods to prevent cancer by stabilizing P53 through non MDM2-mediated pathways |
| EP1812048A4 (en) | 2004-10-20 | 2012-01-18 | Theratechnologies Inc | GH SECRETAGOGA AND ITS USE |
| ES2326750T3 (es) | 2004-10-29 | 2009-10-19 | Schering Corporation | 5-carboxiamido pirazoles y (1,2,4) triazoles como agentes antivirales. |
| US7998930B2 (en) | 2004-11-04 | 2011-08-16 | Hanall Biopharma Co., Ltd. | Modified growth hormones |
| US20060148715A1 (en) | 2004-12-20 | 2006-07-06 | Baylor College Of Medicine | Structural requirements for STAT3 binding and recruitment to phosphotyrosine ligands |
| GB0428187D0 (en) | 2004-12-23 | 2005-01-26 | Univ Liverpool | Cancer treatment |
| SI1844337T1 (sl) | 2005-01-24 | 2013-11-29 | Pepscan Systems B.V. | Povezovalne spojine, imunogene spojine in peptidomimetiki |
| FR2881430B1 (fr) | 2005-02-01 | 2010-10-22 | Servier Lab | Nouveaux peptides interagissant avec les membres anti-apoptotiques de la famille de proteines bcl-2 et utilisations |
| US7759383B2 (en) | 2005-02-22 | 2010-07-20 | The Regents Of The University Of Michigan | Small molecule inhibitors of MDM2 and the uses thereof |
| CA2601577A1 (en) | 2005-03-15 | 2006-09-21 | Allergan, Inc. | Modified clostridial toxins with altered targeting capabilities for clostridial toxin target cells |
| WO2006103666A2 (en) | 2005-03-28 | 2006-10-05 | Yeda Research And Development Co. Ltd. | Isolated bid polypeptides, polynucleotides encoding same and antibodies directed thereagainst and methods of using same for inducing cell cycle arrest or apoptosis |
| WO2006122931A1 (en) | 2005-05-20 | 2006-11-23 | Biovitrum Ab (Publ) | Beta-carboline derivatives and theri use as ghsr modulators |
| JP5122446B2 (ja) * | 2005-06-13 | 2013-01-16 | トランザイム・ファーマ，インコーポレイテッド | 大環状グレリン受容体アンタゴニストおよびインバースアゴニストならびにその使用方法 |
| US20090275648A1 (en) | 2005-06-13 | 2009-11-05 | Fraser Graeme L | Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same |
| US20070020620A1 (en) | 2005-07-14 | 2007-01-25 | Finn M G | Compositions and methods for coupling a plurality of compounds to a scaffold |
| KR20080097382A (ko) | 2005-07-21 | 2008-11-05 | 뉴사우스 이노베이션즈 피티와이 리미티드 | 암의 치료 방법 |
| ES2410132T3 (es) | 2005-07-22 | 2013-07-01 | Ipsen Pharma | Secretagogos de la hormona del crecimiento. |
| EP1757290A1 (en) | 2005-08-16 | 2007-02-28 | Zentaris GmbH | Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors |
| ES2474643T3 (es) | 2005-09-28 | 2014-07-09 | Ipsen Pharma | Análogos de grelina |
| US20070161544A1 (en) | 2006-01-06 | 2007-07-12 | Peter Wipf | Selective targeting agents for mitcochondria |
| WO2007095347A2 (en) | 2006-02-13 | 2007-08-23 | The Gov. Of The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Methods and compositions related to ghs-r antagonists |
| US7538190B2 (en) | 2006-02-17 | 2009-05-26 | Polychip Pharmaceuticals Pty Ltd | Methods for the synthesis of two or more dicarba bridges in organic compounds |
| US7745573B2 (en) | 2006-02-17 | 2010-06-29 | Polychip Pharmaceuticals Pty Ltd. | Conotoxin analogues and methods for synthesis of intramolecular dicarba bridge-containing peptides |
| GB0603295D0 (en) | 2006-02-18 | 2006-03-29 | Ardana Bioscience Ltd | Methods and kits |
| CU23592A1 (es) | 2006-02-28 | 2010-11-11 | Ct Ingenieria Genetica Biotech | Método para prevenir y eliminar las fibrosis y otras formas de depósito patológico en los tejidos aplicando el péptido secretagogo ghrp-6 |
| RU2470940C2 (ru) | 2006-03-13 | 2012-12-27 | Лиат МИНТЦ | Применение варианта сплайсинга грелина для лечения кахексии, и/или анорексии, и/или анорексии-кахексии, и/или нарушения питания, и/или липодистрофии, и/или мышечного истощения, и/или стимуляции аппетита |
| US20100179168A1 (en) | 2006-04-13 | 2010-07-15 | Emma Louise Blaney | Aryl and heteroaryl sulphonamides as growth hormone secretagogue receptor agonists |
| WO2007127457A2 (en) | 2006-04-28 | 2007-11-08 | The Administrators Of The Tulane Educational Fund | Ghrelin/growth hormone releasing peptide/growth hormone secretatogue receptor antagonists and uses thereof |
| GB0611405D0 (en) | 2006-06-09 | 2006-07-19 | Univ Belfast | FKBP-L: A novel inhibitor of angiogenesis |
| US8084022B2 (en) | 2006-06-23 | 2011-12-27 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| US8226949B2 (en) | 2006-06-23 | 2012-07-24 | Aegis Therapeutics Llc | Stabilizing alkylglycoside compositions and methods thereof |
| US20090326193A1 (en) | 2006-06-23 | 2009-12-31 | Aegis Therapeutics Llc | Stabilizing alkylglycoside compositions and methods thereof |
| US8173594B2 (en) | 2006-06-23 | 2012-05-08 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| US7425542B2 (en) | 2006-06-23 | 2008-09-16 | Aegis Therapeutics, Inc. | Stabilizing alkylglycoside compositions and methods thereof |
| US7998927B2 (en) | 2006-06-23 | 2011-08-16 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| JP2009542666A (ja) | 2006-06-30 | 2009-12-03 | シェーリング コーポレイション | Ｐ５３活性を増加させる置換ピペリジンおよびその使用 |
| US8088733B2 (en) | 2006-07-06 | 2012-01-03 | Tranzyme Pharma Inc. | Methods of using macrocyclic agonists of the ghrelin receptor for treatment of gastrointestinal motility disorders |
| WO2008008357A1 (en) | 2006-07-11 | 2008-01-17 | Harkness Pharmaceuticals, Inc. | Methods of treating obesity using satiety factors |
| AU2007277556B2 (en) | 2006-07-26 | 2012-11-29 | Pepscan Systems B.V. | Immunogenic compounds and protein mimics |
| US8614192B2 (en) | 2006-07-28 | 2013-12-24 | Leiden University Medical Center | Method for treating ocular cancer |
| US7737174B2 (en) | 2006-08-30 | 2010-06-15 | The Regents Of The University Of Michigan | Indole inhibitors of MDM2 and the uses thereof |
| EP2099445B1 (en) | 2006-09-04 | 2010-11-17 | University Court of The University of Dundee | P53 activating benzoyl urea and benzoyl thiourea compounds |
| US20080213175A1 (en) | 2006-09-15 | 2008-09-04 | Kolb Hartmuth C | Click chemistry-derived cyclic peptidomimetics as integrin markers |
| US7897394B2 (en) | 2006-09-21 | 2011-03-01 | Intrexon Corporation | Endoplasmic reticulum localization signals |
| JP2010504298A (ja) | 2006-09-21 | 2010-02-12 | エフ．ホフマン−ラ ロシュ アーゲー | オキシンドール誘導体 |
| WO2008039415A2 (en) | 2006-09-27 | 2008-04-03 | Ipsen Pharma S.A.S. | Analogs of ghrelin substituted at the n-terminal |
| ES2387827T3 (es) | 2006-10-05 | 2012-10-02 | New York Blood Center, Inc. | Péptidos antivirales helicoidales, de pequeño tamaño, terapéuticos estabilizados |
| KR100860060B1 (ko) | 2006-10-12 | 2008-09-24 | 한국과학기술연구원 | ＨＩＦ-１α Ｃ-말단 펩타이드와 ＣＢＰ 또는 ｐ３００단백질과의 결합을 정량분석하는 방법 및 상기 방법을이용한 단백질 복합체 형성을 저해하는 억제제의 스크리닝방법 |
| US8691761B2 (en) | 2006-10-16 | 2014-04-08 | Jean E. F. Rivier | Somatostatin receptor 2 antagonists |
| WO2008048942A2 (en) | 2006-10-16 | 2008-04-24 | The Salk Institute For Biological Studies | Receptor(sstr2)-selective somatostatin antagonists |
| EP2489360A1 (en) | 2006-11-15 | 2012-08-22 | Dana-Farber Cancer Institute, Inc. | Stabilized MAML peptides and uses thereof |
| US7932397B2 (en) | 2006-11-22 | 2011-04-26 | Massachusetts Institute Of Technology | Olefin metathesis catalysts and related methods |
| US7981998B2 (en) | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| CN105061577A (zh) | 2006-12-14 | 2015-11-18 | 爱勒让治疗公司 | 双巯基大环化系统 |
| CA2672826A1 (en) | 2006-12-21 | 2008-06-26 | Cytos Biotechnology Ag | Circular ccr5 peptide conjugates and uses thereof |
| ES2425575T3 (es) | 2007-01-29 | 2013-10-16 | Polyphor Ltd. | Peptidomiméticos fijados a una matriz |
| CA2677045C (en) | 2007-01-31 | 2016-10-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| EA200901077A1 (ru) | 2007-02-09 | 2010-04-30 | Транзим Фарма, Инк. | Макроциклические модуляторы грелинового рецептора и их применение |
| CN104086641A (zh) * | 2007-02-23 | 2014-10-08 | 爱勒让治疗公司 | 三唑大环系统 |
| WO2008106507A2 (en) | 2007-02-27 | 2008-09-04 | University Of South Florida | Mdm2/mdmx inhibitor peptide |
| WO2008112941A1 (en) | 2007-03-13 | 2008-09-18 | Board Of Regents The University Of Texas System | Composition and method for the treatment of diseases affected by a peptide receptor |
| CA2682174C (en) | 2007-03-28 | 2021-04-06 | President And Fellows Of Harvard College | Stitched polypeptides |
| TWI429436B (zh) | 2007-04-10 | 2014-03-11 | Helsinn Therapeutics Us Inc | 使用生長激素促泌素治療或預防嘔吐之方法 |
| US20080260820A1 (en) | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| CA2685568A1 (en) | 2007-05-02 | 2008-11-13 | Dana-Farber Cancer Institute, Inc. | Methods of treating diabetes using bad bh3 domain peptide |
| US7879805B2 (en) | 2007-06-01 | 2011-02-01 | Acologix, Inc. | High temperature stable peptide formulation |
| WO2009009727A2 (en) | 2007-07-12 | 2009-01-15 | Akela Pharma Srl | Ghrh analogs and therapeutic uses thereof |
| RU2007133287A (ru) | 2007-09-05 | 2009-03-10 | Ионов Иль Давидович (RU) | Противопсориатическое средство и способ его применения (варианты) |
| CA2699257A1 (en) | 2007-09-11 | 2009-04-16 | Mondobiotech Laboratories Ag | Cgrp as a therapeutic agent |
| WO2009043436A2 (en) | 2007-09-11 | 2009-04-09 | Mondobiotech Laboratories Ag | Use of af12198 as a therapeutic agent |
| JP2010539063A (ja) | 2007-09-11 | 2010-12-16 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | Ｇｒｆ−１（１−２９）および副腎皮質刺激ホルモン放出因子の、治療剤としての使用 |
| US20100298393A1 (en) | 2007-09-17 | 2010-11-25 | Peter Vanderklish | Modulation of Growth Hormone, DHEA, and Cortisol with Positive Modulators of AMPA Type Glutamate Receptors |
| EP2208061B1 (en) | 2007-09-26 | 2017-11-08 | Dana Farber Cancer Institute | Methods and compositions for modulating bcl-2 family polypeptides |
| PL2225271T3 (pl) | 2007-12-03 | 2013-12-31 | Italfarmaco Spa | Nowe nieselektywne analogi somatostatyny |
| WO2009110952A2 (en) | 2007-12-31 | 2009-09-11 | New York University | Control of viral-host membrane fusion with hydrogen bond surrogate-based artificial helices |
| PT2235064E (pt) | 2008-01-07 | 2016-03-01 | Amgen Inc | Método de preparação de moléculas heterodiméricas de fc de anticorpos utilizando efeitos de indução eletrostática |
| CA2712503C (en) | 2008-01-25 | 2017-04-18 | Massachusetts Institute Of Technology | Catalysts for metathesis reactions including enantioselective olefin metathesis, and related methods |
| US9746471B2 (en) | 2008-01-25 | 2017-08-29 | Multivir Inc. | P53 biomarkers |
| CN104474529A (zh) | 2008-02-08 | 2015-04-01 | 爱勒让治疗公司 | 治疗性的拟肽大环化合物 |
| US20090326192A1 (en) * | 2008-04-08 | 2009-12-31 | Aileron Therapeutics, Inc. | Biologically active peptidomimetic macrocycles |
| US20110144303A1 (en) | 2008-04-08 | 2011-06-16 | Aileron Therapeutics, Inc. | Biologically Active Peptidomimetic Macrocycles |
| EP2283033A1 (en) | 2008-05-06 | 2011-02-16 | New York Blood Center | Antiviral cell penetrating peptides |
| US20110250685A1 (en) | 2008-06-03 | 2011-10-13 | Nash Huw M | Compositions and methods for enhancing cellular transport of biomolecules |
| WO2009149339A2 (en) * | 2008-06-05 | 2009-12-10 | University Of Maryland, Baltimore | P53 activator peptides |
| US20110158973A1 (en) | 2008-06-12 | 2011-06-30 | Syntaxin Limited | Suppression of cancers |
| KR101642363B1 (ko) | 2008-06-12 | 2016-07-25 | 입센 바이오이노베이션 리미티드 | 신경내분비계 질환의 억제 |
| CN107446053A (zh) | 2008-06-12 | 2017-12-08 | 益普生生物创新有限公司 | 癌症的抑制 |
| US8796216B2 (en) | 2008-06-12 | 2014-08-05 | Syntaxin Limited | Suppression of neuroendocrine diseases |
| MX2010014078A (es) | 2008-06-25 | 2011-04-11 | Braasch Biotech Llc | Composiciones y metodos para inmunogenecidad mejorada de somatostatina. |
| US20110144306A1 (en) | 2008-07-23 | 2011-06-16 | President And Fellows Of Harvard College | Ligation of stapled polypeptides |
| GB0813873D0 (en) | 2008-07-30 | 2008-09-03 | Univ Dundee | Compounds |
| WO2010033617A2 (en) * | 2008-09-16 | 2010-03-25 | The Research Foundation Of State University Of New York | Stapled peptides and method of synthesis |
| BRPI0919414A2 (pt) | 2008-09-18 | 2017-07-11 | Univ New York | Inibição da interação entre hif-1alfa e p300/cbp com hélices à base de substituintes de ligação de hidrogênio |
| WO2010033240A2 (en) | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Carbohydrate-based drug delivery polymers and conjugates thereof |
| CA2737916A1 (en) * | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP2334697A1 (en) | 2008-09-22 | 2011-06-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2737922A1 (en) | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2010034032A2 (en) | 2008-09-22 | 2010-03-25 | Aileron Therapeutic, Inc. | Methods for preparing purified polypeptide compositions |
| EP2331567A1 (en) | 2008-09-22 | 2011-06-15 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US20120101047A1 (en) | 2008-09-22 | 2012-04-26 | Aileron Therapetics Inc. | Peptidomimetic macrocycles |
| US20110218155A1 (en) | 2008-10-10 | 2011-09-08 | Dana-Farber Cancer Institute, Inc. | Chemical modulators of pro-apoptotic bax and bcl-2 polypeptides |
| JP2010120881A (ja) | 2008-11-19 | 2010-06-03 | Keio Gijuku | ヒト癌タンパク質ＭＤＭ２とヒト癌抑制タンパク質ｐ５３との相互作用阻害ペプチド及びその使用 |
| KR101298168B1 (ko) | 2008-11-21 | 2013-08-20 | 충남대학교산학협력단 | 스네일―ｐ５３ 간의 결합을 저해하는 화합물 및 이를 유효성분으로 함유하는 암질환 치료제 |
| CA2743177A1 (en) | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| WO2010065572A1 (en) | 2008-12-04 | 2010-06-10 | The Salk Institute For Biological Studies | Sstr1-selective analogs |
| JP5731986B2 (ja) | 2008-12-09 | 2015-06-10 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | Ｍｃｌ−１の特異的調節の方法及び組成物 |
| US20100152114A1 (en) | 2008-12-12 | 2010-06-17 | Univ Of Miami And Usa By Dept Of Veterans Affairs | Antioxidant activity of GH-RH Antagonists |
| US9175047B2 (en) | 2009-01-14 | 2015-11-03 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2010083501A2 (en) | 2009-01-16 | 2010-07-22 | University Of South Florida | Alpha-helix mimetic using a 2,5-oligopyrimidine scaffold |
| US8217051B2 (en) | 2009-02-17 | 2012-07-10 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
| US20100239589A1 (en) | 2009-02-23 | 2010-09-23 | Salk Institute For Biological Studies | Methods and Compositions for Ameliorating Diabetes and Symptoms Thereof |
| FR2942798B1 (fr) | 2009-03-05 | 2011-04-08 | Centre Nat Rech Scient | Peptides utilisables pour le traitement de la leucemie lymphoide chronique |
| US20120135089A1 (en) | 2009-03-17 | 2012-05-31 | Stockwell Brent R | E3 ligase inhibitors |
| EP2421548A4 (en) | 2009-04-20 | 2012-09-26 | Theratechnologies Inc | USE OF (HEXENOYL TRANS-3) HGRF (1-44) NH2 AND SIMVASTATIN IN COMBINED TREATMENT |
| US8076482B2 (en) | 2009-04-23 | 2011-12-13 | Hoffmann-La Roche Inc. | 3,3′-spiroindolinone derivatives |
| US8883721B2 (en) | 2009-05-12 | 2014-11-11 | Mcgill University | Methods of inhibiting the ghrelin/growth hormone secretatogue receptor pathway and uses thereof |
| US20100303794A1 (en) | 2009-05-29 | 2010-12-02 | Allergan, Inc. | Methods of Treating Urogenital-Neurological Disorders Using Glucagon Like Hormone Retargeted Endopepidases |
| US20100303791A1 (en) | 2009-05-29 | 2010-12-02 | Allergan, Inc. | Methods of Treating Chronic Neurogenic Inflammation Using Glucagon Like Hormone Retargeted Endopepidases |
| WO2011005219A1 (en) | 2009-07-07 | 2011-01-13 | Agency For Science, Technology And Research | Novel mdm2 binding peptides and uses thereof |
| CA2768299C (en) | 2009-07-13 | 2018-03-20 | President And Fellows Of Harvard College | Bifunctional stapled polypeptides and uses thereof |
| IN2012DN01693A (OSRAM) | 2009-08-26 | 2015-06-05 | Novartis Ag | |
| AU2010298338A1 (en) | 2009-09-22 | 2012-04-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2011041369A1 (en) | 2009-09-30 | 2011-04-07 | Tranzyme Pharma, Inc. | Salts, solvates, and pharmaceutical compositions of macrocyclic ghrelin receptor agonists and methods of using the same |
| WO2011047215A1 (en) | 2009-10-14 | 2011-04-21 | Aileron Therapeutics, Inc. | Improved peptidomimetic macrocycles |
| US8017607B2 (en) | 2009-10-14 | 2011-09-13 | Hoffmann-La Roche Inc. | N-substituted-pyrrolidines as inhibitors of MDM2-P-53 interactions |
| US20110105389A1 (en) | 2009-10-30 | 2011-05-05 | Hoveyda Hamid R | Macrocyclic Ghrelin Receptor Antagonists and Inverse Agonists and Methods of Using the Same |
| WO2011056961A2 (en) | 2009-11-04 | 2011-05-12 | Health Research Inc. | Method and compositions for suppression of aging |
| UA107814C2 (uk) | 2009-11-12 | 2015-02-25 | Дзе Ріджентс Оф Дзе Юніверсіті Оф Мічіган | Спірооксіндольні антагоністи мdм2 |
| US20110118283A1 (en) | 2009-11-17 | 2011-05-19 | Qingjie Ding | Substituted Pyrrolidine-2-Carboxamides |
| US8088815B2 (en) | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| US8658170B2 (en) | 2010-01-06 | 2014-02-25 | Joseph P. Errico | Combination therapy with MDM2 and EFGR inhibitors |
| KR101220516B1 (ko) | 2010-01-21 | 2013-01-10 | 연세대학교 산학협력단 | 항－ｍｄｍ２를 발현하는 인간 성체줄기세포 및 그의 용도 |
| WO2011097642A1 (en) | 2010-02-08 | 2011-08-11 | Trustees Of Boston College | Efficient methods for z- or cis-selective cross-metathesis |
| US8288431B2 (en) | 2010-02-17 | 2012-10-16 | Hoffmann-La Roche Inc. | Substituted spiroindolinones |
| WO2011106650A2 (en) | 2010-02-27 | 2011-09-01 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Novel p53-mdm2/p53-mdm4 antagonists to treat proliferative disease |
| KR20130050938A (ko) | 2010-04-09 | 2013-05-16 | 더 리젠츠 오브 더 유니버시티 오브 미시건 | 질환 치료시 사용하기 위한 ｍｄｍ2 억제제에 대한 바이오마커 |
| WO2011133948A2 (en) | 2010-04-22 | 2011-10-27 | Longevity Biotech, Inc. | Highly active polypeptides and methods of making and using the same |
| JP6121323B2 (ja) | 2010-05-13 | 2017-05-10 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | 核内ホルモン受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| US9145451B2 (en) | 2010-05-13 | 2015-09-29 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhbiting G protein coupled receptor activity |
| WO2011153491A2 (en) | 2010-06-03 | 2011-12-08 | University Of Miami | Agonists of growth hormone releasing hormone as effectors for survival and proliferation of pancreatic islets |
| WO2011159917A2 (en) | 2010-06-16 | 2011-12-22 | The Administrators Of The Tulane Educational Fund | Growth hormone secretatogue receptor antagonists and uses thereof |
| US20130177979A1 (en) | 2010-06-22 | 2013-07-11 | University Of Central Florida Research Foundation, Inc. | Methods and compositions for cell permeable stat3 inhibitor |
| US20110313167A1 (en) | 2010-06-22 | 2011-12-22 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Substituted Heterocycles as Therapeutic agents for treating cancer |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| JP6101202B2 (ja) | 2010-06-24 | 2017-03-22 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | ジペプチド結合医薬剤 |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| US20130137645A1 (en) | 2010-07-19 | 2013-05-30 | Mary S. Rosendahl | Modified peptides and proteins |
| WO2012016186A1 (en) | 2010-07-29 | 2012-02-02 | President And Fellows Of Harvard College | Macrocyclic kinase inhibitors and uses thereof |
| WO2012021875A1 (en) | 2010-08-13 | 2012-02-16 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with triazole linkers |
| CA2810499A1 (en) | 2010-09-08 | 2012-03-15 | University Of Pittsburgh - Of The Commonwealth System Of Higher Educatio N | P53-mdm2 antagonists |
| US20120065210A1 (en) | 2010-09-15 | 2012-03-15 | Xin-Jie Chu | Substituted hexahydropyrrolo[1,2-c]imidazolones |
| WO2012037519A2 (en) | 2010-09-16 | 2012-03-22 | University Of Miami | Acceleration of wound healing by growth hormone releasing hormone and its agonists |
| EP2431035A1 (en) | 2010-09-16 | 2012-03-21 | Æterna Zentaris GmbH | Novel Triazole Derivatives with Improved Receptor Activity and Bioavailability Properties as Ghrelin Antagonists of Growth Hormone Secretagogue Receptors |
| CN102399283B (zh) | 2010-09-17 | 2013-05-29 | 中国农业大学 | 水貂生长激素释放激素cDNA及其应用 |
| CN102399284B (zh) | 2010-09-17 | 2013-05-29 | 中国农业大学 | 狐狸生长激素释放激素cDNA及其应用 |
| US20120071499A1 (en) | 2010-09-20 | 2012-03-22 | Xin-Jie Chu | Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones |
| WO2012040459A2 (en) | 2010-09-22 | 2012-03-29 | President And Fellows Of Harvard College | Beta-catenin targeting peptides and uses thereof |
| US20130225603A1 (en) | 2010-09-27 | 2013-08-29 | Serrata Llc | Mdm2 inhibitors for treatment of ocular conditions |
| ES2685175T3 (es) | 2010-09-30 | 2018-10-05 | St. Jude Children's Research Hospital | Imidazoles sustituidos con arilo |
| WO2012051405A1 (en) | 2010-10-13 | 2012-04-19 | Bristol-Myers Squibb Company | Methods for preparing macrocycles and macrocycle stabilized peptides |
| FR2967072B1 (fr) | 2010-11-05 | 2013-03-29 | Univ Dundee | Procede pour ameliorer la production de virus et semences vaccinales influenza |
| CA2817568A1 (en) | 2010-11-12 | 2012-05-18 | The Salk Institute For Biological Studies Intellectual Property And Tech Nology Transfer | Cancer therapies and diagnostics |
| WO2012065022A2 (en) | 2010-11-12 | 2012-05-18 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
| WO2012076513A1 (en) | 2010-12-09 | 2012-06-14 | F. Hoffmann-La Roche Ag | 3-cyano-1-hydroxymethyl-2-phenylpyrrolidine derivatives as inhibitors of mdm2-p53 interactions useful for the treatment of cancer |
| EP2651964B1 (en) | 2010-12-15 | 2018-02-28 | The Research Foundation of State University of New York | Cross-linked peptides and proteins, methods of making same, and uses thereof |
| WO2012080389A1 (en) | 2010-12-16 | 2012-06-21 | Roche Glycart Ag | Combination therapy of an afucosylated cd20 antibody with a mdm2 inhibitor |
| WO2012083181A1 (en) | 2010-12-16 | 2012-06-21 | Indiana University Research And Technology Corporation | Alpha helix mimetics and methods for using |
| EP2651921A1 (en) | 2010-12-17 | 2013-10-23 | Syngenta Participations AG | Insecticidal compounds |
| EP2474624B1 (en) | 2011-01-05 | 2016-08-17 | Daniela Kandioler | Response prediction in cancer treatment (p53 adapted cancer therapy) |
| EP2474625B1 (en) | 2011-01-05 | 2016-11-02 | Daniela Kandioler | Method for determining the p53 status of a tumour |
| WO2012094755A1 (en) | 2011-01-14 | 2012-07-19 | Theratechnologies Inc. | Assessment of igf-1 levels in hiv-infected subjects and uses thereof |
| CA2828889A1 (en) | 2011-03-04 | 2012-09-13 | New York University | Hydrogen bond surrogate macrocycles as modulators of ras |
| DK2684888T3 (da) | 2011-03-09 | 2019-08-19 | Jitsubo Co Ltd | Nye tværbundne peptider indeholdende ikke-peptid-tværbundet struktur, fremgangsmåde til syntetisering af tværbundne peptider og ny organisk forbindelse anvendt i fremgangsmåden |
| MY172862A (en) | 2011-03-10 | 2019-12-13 | Daiichi Sankyo Co Ltd | Dispiropyrrolidine derivatives |
| EP2701725A1 (en) | 2011-04-29 | 2014-03-05 | Kinemed, Inc. | Chemical modification of apolipoprotein mimetic peptides for the production of therapeutic agents |
| WO2012173846A2 (en) | 2011-06-06 | 2012-12-20 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2012174409A1 (en) | 2011-06-17 | 2012-12-20 | President And Fellows Of Harvard College | Stabilized variant maml peptides and uses thereof |
| US9487562B2 (en) | 2011-06-17 | 2016-11-08 | President And Fellows Of Harvard College | Stabilized polypeptides as regulators of RAB GTPase function |
| GB201110390D0 (en) | 2011-06-20 | 2011-08-03 | Medical Res Council | Compounds for use in stabilising p53 mutants |
| US20120328692A1 (en) | 2011-06-24 | 2012-12-27 | University Of Maryland, Baltimore | Potent d-peptide antagonists of mdm2 and mdmx for anticancer therapy |
| WO2013033645A1 (en) | 2011-08-31 | 2013-03-07 | New York University | Thioether-,ether-, and alkylamine-linked hydrogen bond surrogate pertidomimentics |
| US9517252B2 (en) | 2011-09-09 | 2016-12-13 | Agency For Science, Technology And Research | p53 activating peptides |
| WO2013049250A1 (en) | 2011-09-27 | 2013-04-04 | Amgen Inc. | Heterocyclic compounds as mdm2 inhibitors for the treatment of cancer |
| CN108929375A (zh) | 2011-10-18 | 2018-12-04 | 爱勒让治疗公司 | 拟肽大环化合物 |
| WO2013059530A2 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2013062923A1 (en) | 2011-10-28 | 2013-05-02 | Merck Sharp & Dohme Corp. | MACROCYCLES THAT INCREASE p53 ACTIVITY AND THE USES THEREOF |
| US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
| CA2761253A1 (en) | 2011-12-07 | 2013-06-07 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| CN112500466B (zh) | 2012-02-15 | 2022-05-03 | 艾瑞朗医疗公司 | 拟肽大环化合物 |
| US9880171B2 (en) | 2012-03-02 | 2018-01-30 | Ludwig Institute For Cancer Research Ltd. | iASPP phosphorylation and metastatic potential |
| US9216170B2 (en) | 2012-03-19 | 2015-12-22 | Hoffmann-La Roche Inc. | Combination therapy for proliferative disorders |
| SMT202100337T1 (it) | 2012-09-26 | 2021-07-12 | Harvard College | Peptidi graffati bloccati con prolina e loro usi |
| WO2014055564A1 (en) | 2012-10-01 | 2014-04-10 | President And Fellows Of Harvard College | Stabilized polypeptide insulin receptor modulators |
| CN104812384B (zh) | 2012-11-01 | 2020-09-18 | 爱勒让治疗公司 | 二取代的氨基酸及其制备和使用方法 |
| WO2014138429A2 (en) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating hif1alpha |
| JP6568515B2 (ja) | 2013-03-13 | 2019-08-28 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ステープルドおよびステッチドポリペプチドならびにその使用 |
| US9198910B2 (en) | 2013-04-04 | 2015-12-01 | The Translational Genomics Research Institute | Methods for the treatment of cancer |
| CN105492460A (zh) | 2013-06-14 | 2016-04-13 | 哈佛大学的校长及成员们 | 稳定化多肽胰岛素受体调控剂 |
| CA2919837A1 (en) | 2013-08-02 | 2015-02-05 | Children's Hospital Medical Center | Compositions and methods for treating disease states associated with activated t cells and/or b cells |
| WO2015051030A2 (en) | 2013-10-01 | 2015-04-09 | President And Fellows Of Harvard College | Stabilized polypeptides and uses thereof |
| DK3068393T5 (da) | 2013-11-11 | 2022-08-22 | Amgen Inc | Kombinationsterapi som inkluderer en mdm2-inhibitor og et eller flere yderligere farmaceutisk aktive midler til behandlingen af kræftformer |
| RS60142B1 (sr) | 2013-12-05 | 2020-05-29 | Hoffmann La Roche | Novi kombinovani tretman za akutnu mijeloidnu leukemiju (aml) |
| KR20160100975A (ko) | 2013-12-23 | 2016-08-24 | 노파르티스 아게 | 제약 조합물 |
| US20170037086A1 (en) | 2014-04-09 | 2017-02-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with pth activity |
| TW201613576A (en) | 2014-06-26 | 2016-04-16 | Novartis Ag | Intermittent dosing of MDM2 inhibitor |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| EP3197478A4 (en) | 2014-09-24 | 2018-05-30 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| SG11201707750YA (en) | 2015-03-20 | 2017-10-30 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| KR20180022971A (ko) | 2015-07-02 | 2018-03-06 | 다나-파버 캔서 인스티튜트 인크. | 안정화된 항미생물성 펩티드 |
| US20170037105A1 (en) | 2015-08-03 | 2017-02-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP3344275B8 (en) | 2015-09-03 | 2023-04-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN108368161A (zh) | 2015-09-10 | 2018-08-03 | 艾瑞朗医疗公司 | 作为mcl-1调节剂的拟肽大环化合物 |
| KR20180128022A (ko) | 2016-03-21 | 2018-11-30 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드 모방 거대고리에 대한 동반 진단 도구 |
| WO2017205786A1 (en) | 2016-05-27 | 2017-11-30 | Aileron Therapeutics, Inc. | Cell permeable peptidomimetic macrocycles |
| WO2017218949A2 (en) | 2016-06-17 | 2017-12-21 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2018165575A2 (en) | 2017-03-09 | 2018-09-13 | Aileron Therapeutics, Inc. | Warhead-containing peptidomimetic macrocycles as modulators of bfl-1 |
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