ES2970913T3 - Oxabicicloheptanos para modulación de la respuesta inmunitaria - Google Patents
Oxabicicloheptanos para modulación de la respuesta inmunitaria Download PDFInfo
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- ES2970913T3 ES2970913T3 ES17879038T ES17879038T ES2970913T3 ES 2970913 T3 ES2970913 T3 ES 2970913T3 ES 17879038 T ES17879038 T ES 17879038T ES 17879038 T ES17879038 T ES 17879038T ES 2970913 T3 ES2970913 T3 ES 2970913T3
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| MX393461B (es) | 2015-05-15 | 2025-03-24 | Lixte Biotechnology Inc | Farmacos precursores de oxabicicloheptanos |
| ES2970913T3 (es) | 2016-12-08 | 2024-05-31 | Lixte Biotechnology Inc | Oxabicicloheptanos para modulación de la respuesta inmunitaria |
| KR102723511B1 (ko) | 2019-08-13 | 2024-10-28 | 주식회사 엘지에너지솔루션 | 전극 스크랩 재활용 방법 및 이를 이용한 전극 제조 방법 |
| US20240052050A1 (en) * | 2020-12-16 | 2024-02-15 | Merus N.V. | Multispecific antibodies for the treatment of cancer |
| JP2024504586A (ja) * | 2021-01-19 | 2024-02-01 | リクスト・バイオテクノロジー,インコーポレイテッド | 小細胞肺がんの処置のためのオキサビシクロヘプタン |
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Family Cites Families (187)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2957906A (en) | 1955-10-25 | 1960-10-25 | Monsanto Chemicals | Ketones |
| US3227473A (en) | 1963-12-12 | 1966-01-04 | Julian S Halbern | Check identification |
| JPS5752354B2 (enExample) | 1973-10-22 | 1982-11-06 | ||
| JPS5069091U (enExample) | 1973-10-25 | 1975-06-19 | ||
| US3980674A (en) | 1974-01-28 | 1976-09-14 | Delmar Chemicals Limited | 2,3-Disubstituted 7-oxabicyclo-[2.2.1]-5-heptene |
| JPS5132733A (en) | 1974-09-10 | 1976-03-19 | Kyowa Hakko Kogyo Kk | Josozai |
| US3954913A (en) | 1975-01-06 | 1976-05-04 | The Standard Oil Company | Stabilized nitrile polymers |
| JPS5188631U (enExample) | 1975-01-10 | 1976-07-15 | ||
| JPS5188631A (en) | 1975-01-31 | 1976-08-03 | Hiiryoyosatsukinzai oyobi sonoseizoho | |
| US4143054A (en) | 1977-11-04 | 1979-03-06 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane- and 7-oxabicycloheptene compounds |
| US4218478A (en) | 1979-01-05 | 1980-08-19 | Ruiko Oiwa | Trichostatin as an antiprotozoal agent |
| US4760067A (en) | 1979-08-15 | 1988-07-26 | Merck & Co., Inc. | Allylsulfoxide enzyme inhibitors |
| US4298752A (en) | 1980-09-19 | 1981-11-03 | Regents Of The University Of California | Cycloadduct precursors of cantharidin and method |
| US4614825A (en) | 1982-05-17 | 1986-09-30 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane and 7-oxabicycloheptene compounds |
| US4463015A (en) | 1982-08-18 | 1984-07-31 | E. R. Squibb & Sons, Inc. | Aryl substituted 7-oxabicycloheptane compounds, useful in inhibiting platelet aggregation |
| US4518696A (en) | 1983-01-11 | 1985-05-21 | Chr. Hansen's Laboratory, Inc. | Stabilized liquid bacterial suspension for oral administration to animals |
| US4524151A (en) | 1983-11-14 | 1985-06-18 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane thio ethers useful as cardiovascular agents |
| JPS61176523A (ja) | 1985-01-30 | 1986-08-08 | Teruhiko Beppu | 制癌剤 |
| US4654355A (en) | 1985-08-01 | 1987-03-31 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane substituted amide-thioamide prostaglandin analogs |
| US4851553A (en) | 1986-06-04 | 1989-07-25 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane amido-carboxylic acids |
| US4816579A (en) | 1986-06-04 | 1989-03-28 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane amino-alcohol intermediates useful in making thromboxane A2 receptor antagonists |
| US4851423A (en) | 1986-12-10 | 1989-07-25 | Schering Corporation | Pharmaceutically active compounds |
| SU1553533A1 (ru) | 1988-01-28 | 1990-03-30 | Военная Краснознаменная академия химической защиты им.Маршала Советского Союза С.К.Тимошенко | Способ получени 1,4-бисполифторалкил-7-оксбицикло [2.2.1]гептанов |
| JP2789365B2 (ja) | 1988-12-14 | 1998-08-20 | 塩野義製薬株式会社 | ジカルボン酸モノエステルおよびその製造法 |
| RU2015980C1 (ru) | 1990-02-06 | 1994-07-15 | Е.Р.Сквибб энд Санз, Инк. | 7-оксабициклогептилзамещенные гетероциклические амиды или их стереоизомеры в качестве антагонистов рецепторов тромбоксана |
| US5763647A (en) | 1990-03-30 | 1998-06-09 | Shionogi & Co., Ltd. | Preparation of optically active 1,4-bridged-cyclohexane carboxylic acid derivatives |
| WO1991018891A1 (en) | 1990-06-04 | 1991-12-12 | Pfizer Inc. | Aromatic pyrrolidine and thiazolidine amides |
| US5229115A (en) | 1990-07-26 | 1993-07-20 | Immunex Corporation | Adoptive immunotherapy with interleukin-7 |
| US5266710A (en) | 1990-12-18 | 1993-11-30 | Patel Ramesh N | (Exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol; monoacyl ester and diacyl ester |
| US5206386A (en) | 1991-03-20 | 1993-04-27 | Isp Investments Inc. | Controlled release N-substituted pyrrolidone esters and process for the use thereof |
| US5580858A (en) | 1991-06-10 | 1996-12-03 | Alberta Research Council | Immunosuppressive and tolerogenic modified Lewisx compounds |
| JP3134233B2 (ja) | 1991-07-26 | 2001-02-13 | 株式会社林原生物化学研究所 | α−グリコシル ケルセチンとその製造方法並びに用途 |
| US5326898A (en) | 1992-02-11 | 1994-07-05 | Allergan, Inc. | Substituted phenylethenyl compounds having retinoid-like biological activity |
| US6602713B1 (en) | 2001-02-09 | 2003-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of protein phosphatase 2 catalytic subunit beta expression |
| US5580856A (en) | 1994-07-15 | 1996-12-03 | Prestrelski; Steven J. | Formulation of a reconstituted protein, and method and kit for the production thereof |
| US5518993A (en) | 1994-08-12 | 1996-05-21 | Buckman Laboratories International, Inc. | Pesticidal compositions containing ethoxylated fatty amines for increasing the effectiveness of endothal and salts thereof |
| US5770382A (en) | 1994-12-30 | 1998-06-23 | Ligand Pharmaceuticals, Inc. | Tricyclic retinoids, methods for their production and use |
| US6222055B1 (en) | 1995-07-06 | 2001-04-24 | Fraunhofer-Gesellschaft Zur Foerderung Der Angwandten Forschung E.V. | Hydrolyzable and polymerizable and/or polyadditive silanes |
| DE19600707B4 (de) | 1996-01-11 | 2004-02-19 | Glüsenkamp, Karl-Heinz, Dr. | Biyclische Anhydrid-Wirkstoff-Verbindungen, Verfahren zur Herstellung und Verwendung derselben |
| US5968965A (en) | 1996-01-30 | 1999-10-19 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US6777217B1 (en) | 1996-03-26 | 2004-08-17 | President And Fellows Of Harvard College | Histone deacetylases, and uses related thereto |
| US5925651A (en) | 1996-04-03 | 1999-07-20 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US6387673B1 (en) | 1997-05-01 | 2002-05-14 | The Salk Institute For Biological Studies | Compounds useful for the modulation of processes mediated by nuclear hormone receptors, methods for the identification and use of such compounds |
| WO1999018798A1 (en) | 1997-10-15 | 1999-04-22 | Polarx Biopharmaceuticals, Inc. | Compositions and methods for the treatment of primary and metastatic neoplastic diseases using arsenic compounds |
| US6632823B1 (en) | 1997-12-22 | 2003-10-14 | Merck & Co., Inc. | Substituted pyridine compounds useful as modulators of acetylcholine receptors |
| US6262116B1 (en) | 1998-01-23 | 2001-07-17 | Sloan-Kettering Institute For Cancer Research | Transcription therapy for cancers |
| ATE413889T1 (de) | 1998-06-05 | 2008-11-15 | Nutrinia Ltd | Insulin angereichertes säuglingsnährpräparat |
| US20040110822A1 (en) | 1998-07-14 | 2004-06-10 | The University Of Newcastle Research Associates | Anhydride modified cantharidin analogues useful in the treatment of cancer |
| AUPP466598A0 (en) | 1998-07-14 | 1998-08-06 | University Of Newcastle Research Associates Limited, The | Product and process |
| PT1102763E (pt) | 1998-08-07 | 2005-01-31 | Applied Research Systems | Mimeticos fsh para o tratamento da infertilidade |
| US20020151515A1 (en) | 1999-06-18 | 2002-10-17 | Roberts Bruce L. | Preparation and use of superior vaccines |
| US6949624B1 (en) | 1999-08-03 | 2005-09-27 | The United States Of America As Represented By The Department Of Health And Human Services | Cloning of the human nuclear receptor co-repressor gene |
| CA2383999A1 (en) | 1999-09-08 | 2001-03-15 | Sloan-Kettering Institute For Cancer Research | Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof |
| US7605185B2 (en) | 1999-11-23 | 2009-10-20 | Gerhart Graupner | Treatment of arrhythmia by retinoids affecting signal transduction |
| WO2001062242A1 (en) | 2000-02-24 | 2001-08-30 | Biocryst Pharmaceuticals, Inc. | Prodrugs of substituted cyclopentane and cyclopentene compounds useful as neuraminidase inhibitors |
| JP4518627B2 (ja) | 2000-03-14 | 2010-08-04 | 旭化成イーマテリアルズ株式会社 | ヒドロキシポリアミド |
| CA2404002A1 (en) | 2000-03-24 | 2001-09-27 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| DE10038043B4 (de) | 2000-08-02 | 2006-09-07 | Walter, Michael, Dr. | Phamakologisch wirksame Substanz zur Behandlung kardiovaskulärer Erkrankungen |
| PE20020354A1 (es) | 2000-09-01 | 2002-06-12 | Novartis Ag | Compuestos de hidroxamato como inhibidores de histona-desacetilasa (hda) |
| US7199137B2 (en) | 2000-09-21 | 2007-04-03 | Smithkline Beecham Plc | Imidazole derivatives as Raf kinase inhibitors |
| US6696483B2 (en) | 2000-10-03 | 2004-02-24 | Oncopharmaceutical, Inc. | Inhibitors of angiogenesis and tumor growth for local and systemic administration |
| AU2001296661A1 (en) | 2000-10-06 | 2002-04-15 | Michigan State University | Divinyl ether synthase gene and protein, and uses thereof |
| CN1213050C (zh) | 2000-11-23 | 2005-08-03 | 拜尔公司 | 氧杂双环[2.2.1]庚烷衍生物,其制备方法和作为农药的用途 |
| US20020177692A1 (en) | 2001-04-16 | 2002-11-28 | Myriad Genetics, Incorporated | BCL-XL-interacting protein and use thereof |
| WO2002066045A2 (en) | 2001-02-16 | 2002-08-29 | Genetics Institute, Llc. | Methods for modulating an immune response by modulating the interaction between ctla4 and pp2a |
| AUPR392301A0 (en) | 2001-03-23 | 2001-04-26 | University Of Newcastle Research Associates Limited, The | Protein phosphatase inhibitors |
| US20040253637A1 (en) | 2001-04-13 | 2004-12-16 | Biosite Incorporated | Markers for differential diagnosis and methods of use thereof |
| US6905669B2 (en) | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| DE10122898A1 (de) | 2001-05-11 | 2002-11-14 | Haarmann & Reimer Gmbh | Verwendung von Hydroxyflavanonen zur Maskierung des bitteren Geschmacks |
| US20070015144A9 (en) | 2001-05-25 | 2007-01-18 | Genset, S.A. | Human cDNAs and proteins and uses thereof |
| US7528274B2 (en) | 2001-08-03 | 2009-05-05 | The United States Of America As Represented By The Department Of Health And Human Services | Acylthiols and component thiol compositions as anti-HIV and anti-retroviral agents |
| US20040010045A1 (en) | 2001-09-07 | 2004-01-15 | Taolin Yi | Therapeutic compositions comprised of pentamidine and methods of using same to treat cancer |
| US7179450B2 (en) | 2001-09-20 | 2007-02-20 | Medi-Physics, Inc. | Methods for in vivo evaluation of pulmonary physiology and/or function using NMR signals of polarized Xe |
| ATE517624T1 (de) | 2001-10-16 | 2011-08-15 | Sloan Kettering Inst Cancer | Behandlung von neurodegenerativen erkrankungen und krebs im gehirn |
| PT1443967E (pt) | 2001-11-06 | 2007-04-30 | Novartis Ag | Combinação de inibidor da ciclooxigenase-2/inibidor da histona-desacetilase |
| AU2002353845A1 (en) | 2001-11-23 | 2003-06-10 | Eli Lilly And Company | Prodrugs of excitatory amino acids |
| JP2004035408A (ja) | 2002-02-15 | 2004-02-05 | Chiron Corp | テザシタビンを含有する安定な組成物 |
| CN1646558B (zh) | 2002-02-20 | 2010-05-12 | 国立大学法人九州工业大学 | 组蛋白脱乙酰酶抑制剂 |
| US7456219B2 (en) | 2002-03-04 | 2008-11-25 | Merck Hdac Research, Llc | Polymorphs of suberoylanilide hydroxamic acid |
| US7148257B2 (en) | 2002-03-04 | 2006-12-12 | Merck Hdac Research, Llc | Methods of treating mesothelioma with suberoylanilide hydroxamic acid |
| CA2478587C (en) | 2002-03-08 | 2011-05-17 | Basf Aktiengesellschaft | Fungicidal mixtures based on prothioconazole and containing an insecticide |
| US6809118B2 (en) | 2002-07-25 | 2004-10-26 | Yih-Lin Chung | Methods for therapy of radiation cutaneous syndrome |
| IL149404A0 (en) | 2002-04-29 | 2002-11-10 | Yissum Res Dev Co | METHODS AND COMPOSITIONS FOR MODULATING β-CATENIN PHOSPHORYLATION |
| WO2003092616A2 (en) | 2002-05-01 | 2003-11-13 | The Cleveland Clinic Foundation | Therapeutic compositions comprised of pentamidine and methods of using same to treat cancer |
| WO2003097835A2 (en) | 2002-05-16 | 2003-11-27 | Molecular Engines Laboratories | Pharmaceutical compositions for the treatment of cancer |
| US7186740B2 (en) | 2002-09-23 | 2007-03-06 | Schering Corporation | Imidazopyrazines as cyclin dependent kinase inhibitors |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7189740B2 (en) | 2002-10-15 | 2007-03-13 | Celgene Corporation | Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes |
| US8404716B2 (en) | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
| EP1567860A4 (en) | 2002-11-05 | 2006-05-10 | Univ California | METHOD AND MATERIALS FOR THE INVESTIGATION OF PATHS ASSOCIATED WITH GLOBALBLASTOM PROGRESSION |
| GB0226855D0 (en) | 2002-11-18 | 2002-12-24 | Queen Mary & Westfield College | Histone deacetylase inhibitors |
| MXPA05006828A (es) | 2002-12-23 | 2005-09-08 | Wyeth Corp | Anticuerpos contra pd-1, y sus usos. |
| US20040197888A1 (en) | 2002-12-31 | 2004-10-07 | Armour Christopher D. | Alternatively spliced isoforms of histone deacetylase 3 (HDAC3) |
| US20050222013A1 (en) | 2003-01-16 | 2005-10-06 | Georgetown University | Methods for the use of inhibitors of histone deacetylase as synergistic agents in cancer therapy |
| US8802116B2 (en) | 2003-02-27 | 2014-08-12 | Novasel Australia Pty. Ltd. | Poloxamer emulsion preparations |
| JP2006519609A (ja) | 2003-03-12 | 2006-08-31 | サマリタン・ファーマシューティカルズ・インコーポレイテッド | 神経疾患擬態動物モデル |
| US7893096B2 (en) | 2003-03-28 | 2011-02-22 | Novartis Vaccines And Diagnostics, Inc. | Use of small molecule compounds for immunopotentiation |
| US7842835B2 (en) | 2003-07-07 | 2010-11-30 | Georgetown University | Histone deacetylase inhibitors and methods of use thereof |
| WO2005025620A2 (en) | 2003-08-13 | 2005-03-24 | Pharmacia Corporation | Combination therapy with inhibitors of inducible nitric oxide synthase and alkylating agents |
| EP1653960A4 (en) | 2003-08-13 | 2008-11-26 | Amgen Inc | MELANIN CONCENTRATION HORMONE RECEPTOR ANTAGONIST |
| CA2535585A1 (en) | 2003-08-21 | 2005-03-03 | Osaka University | Pharmaceutical composition for preventing or remedying cardiac hypertrophy and cardiocascular disease caused thereby |
| US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7094193B2 (en) | 2003-08-28 | 2006-08-22 | Philip Morris Usa Inc. | High speed laser perforation of cigarette tipping paper |
| JP2007507549A (ja) | 2003-10-06 | 2007-03-29 | グラクソ グループ リミテッド | キナーゼ阻害剤としての1,6,7−三置換アザベンゾイミダゾールの調製 |
| US20070208166A1 (en) | 2003-10-24 | 2007-09-06 | Exelixis, Inc. | Tao Kinase Modulators And Method Of Use |
| CA2545944A1 (en) | 2003-11-13 | 2005-06-02 | Board Of Regents, The University Of Texas System | Inhibition of trp channels as a treatment for cardiac hypertrophy and heart failure |
| GB0328157D0 (en) | 2003-12-04 | 2004-01-07 | Imp College Innovations Ltd | Compounds |
| US20060018970A1 (en) | 2003-12-12 | 2006-01-26 | Myogen, Inc. | Enoximone formulations and their use in the treatment of cardiac hypertrophy and heart failure |
| US8652502B2 (en) | 2003-12-19 | 2014-02-18 | Cordis Corporation | Local vascular delivery of trichostatin A alone or in combination with sirolimus to prevent restenosis following vascular injury |
| US20050282893A1 (en) | 2004-01-30 | 2005-12-22 | Au Jessie L | Methods and compositions for using suramin, pentosan, polysulfate, telomerase antisense and telomerase inhibitors |
| CA2555632A1 (en) | 2004-02-02 | 2005-08-18 | Myogen, Inc. | Inhibition of protein kinase c-related kinase (prk) as a treatment for cardiac hypertrophy and heart failure |
| US7253204B2 (en) | 2004-03-26 | 2007-08-07 | Methylgene Inc. | Inhibitors of histone deacetylase |
| FR2872704B1 (fr) | 2004-07-12 | 2007-11-02 | Laurent Schwartz | Pluritherapie contre le cancer |
| CN1586500A (zh) | 2004-07-19 | 2005-03-02 | 俞锋 | 治疗肿瘤的斑蝥酸钠注射剂及其制备方法 |
| CN101106997A (zh) | 2004-08-17 | 2008-01-16 | 约翰·霍普金斯大学 | Pde5抑制剂组合物及治疗心脏病征候的方法 |
| WO2006052842A2 (en) | 2004-11-09 | 2006-05-18 | The Trustees Of The University Of Pennsylvania | Methods for diagnosis of myelodysplastic syndromes (mds) |
| KR100677149B1 (ko) | 2004-11-12 | 2007-02-02 | 삼성전자주식회사 | 잉크 조성물 |
| AU2006228957A1 (en) | 2005-04-01 | 2006-10-05 | Methylgene Inc. | Inhibitors of histone deacetylase |
| CN1304396C (zh) | 2005-04-08 | 2007-03-14 | 中山大学 | 斑蝥素衍生物及其制备方法 |
| JP4361545B2 (ja) | 2005-05-09 | 2009-11-11 | 小野薬品工業株式会社 | ProgrammedDeath1(PD−1)に対するヒトモノクローナル抗体および抗PD−1抗体単独または他の免疫療法と併用した癌治療方法 |
| GB0511266D0 (en) | 2005-06-02 | 2005-07-13 | Trust | Chemical compounds |
| HRP20151102T1 (xx) | 2005-07-01 | 2015-11-20 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska antitijela za ligand programirane smrti 1 (pd-l1) |
| WO2007014033A2 (en) | 2005-07-22 | 2007-02-01 | The Regents Of The University Of Colorado, A Body Corporate | Inhibition of extracellular signal-regulated kinase 1/2 as a treatment for cardiac hypertrophy and heart failure |
| MX2008001964A (es) | 2005-08-10 | 2008-03-26 | Novartis Ag | Metodo de uso de inhibidores de desacetilasa. |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| US20070092553A1 (en) | 2005-10-21 | 2007-04-26 | Pfab Lp | Compositions and methods of making rapidly dissolving lonically masked formulations |
| CA2633010A1 (en) | 2005-12-19 | 2007-06-28 | Methylgene Inc. | Histone deacetylase inhibitors for enhancing activity of antifungal agents |
| WO2007092414A2 (en) | 2006-02-06 | 2007-08-16 | Lixte Biotechnology Holdings, Inc. | Use of phosphatases to treat tumors overexpressing n-cor |
| CA2648804C (en) | 2006-04-07 | 2014-05-27 | Methylgene Inc. | Benzamide derivatives as inhibitors of histone deacetylase |
| AR060635A1 (es) | 2006-04-27 | 2008-07-02 | Banyu Pharma Co Ltd | Derivados de 1,2-dihidro-3h-pirazolo[3,4-d]pirimidin-3-ona, composiciones farmaceuticas que los comprenden y su uso en el tratamiento del cancer |
| US20090018142A9 (en) | 2006-05-02 | 2009-01-15 | Zhengping Zhuang | Use of phosphatases to treat tumors overexpressing N-CoR |
| US20080267947A1 (en) | 2006-09-07 | 2008-10-30 | Cirrito Thomas P | Cancer therapy with cantharidin and cantharidin analogs |
| US8129340B2 (en) | 2006-09-08 | 2012-03-06 | Institut Gustave Roussy | Inhibitors of protein phosphatase 1, GADD34 and protein phosphatase 1/GADD34 complex, preparation and uses thereof |
| US20080097561A1 (en) | 2006-10-18 | 2008-04-24 | Medcool, Inc. | Dual cycle thermal system and method of use |
| AU2007321720A1 (en) | 2006-11-15 | 2008-05-22 | Genetic Technologies Limited | Compounds, compositions and methods for controlling invertebrate pests |
| JP5693850B2 (ja) | 2007-02-06 | 2015-04-01 | リクスト・バイオテクノロジー,インコーポレイテッド | オキサビシクロヘプタンおよびオキサビシクロヘプテン、それらの製造および使用 |
| US8413445B2 (en) | 2007-05-11 | 2013-04-09 | General Electric Company | Method and system for porous flame holder for hydrogen and syngas combustion |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| AU2008284364A1 (en) | 2007-08-03 | 2009-02-12 | Lixte Biotechnology, Inc. | Use of phosphatases to treat neuroblastomas and medulloblastomas |
| ES2628748T3 (es) | 2007-10-01 | 2017-08-03 | Lixte Biotechnology, Inc. | Inhibidores de la HDAC |
| JP5069091B2 (ja) | 2007-12-12 | 2012-11-07 | 三菱電機株式会社 | 監視カメラおよび監視カメラシステム |
| CA2715166C (en) | 2008-02-11 | 2017-05-16 | Curetech Ltd. | Monoclonal antibodies for tumor treatment |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| WO2010014220A1 (en) | 2008-08-01 | 2010-02-04 | Lixte Biotechnology, Inc. | Neuroprotective agents for the prevention and treatment of neurodegenerative diseases |
| US8227473B2 (en) * | 2008-08-01 | 2012-07-24 | Lixte Biotechnology, Inc. | Oxabicycloheptanes and oxabicycloheptenes, their preparation and use |
| CA2730428A1 (en) | 2008-08-01 | 2010-02-04 | Lixte Biotechnology, Inc. | Methods for regulating cell mitosis by inhibiting serine/threonine phosphatase |
| WO2010147612A1 (en) | 2009-06-18 | 2010-12-23 | Lixte Biotechnology, Inc. | Methods of modulating cell regulation by inhibiting p53 |
| CN102203132A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂的组合物和使用方法 |
| JP2012510429A (ja) | 2008-08-25 | 2012-05-10 | アンプリミューン、インコーポレーテッド | Pd−1アンタゴニストおよびその使用方法 |
| CN101367783A (zh) | 2008-10-10 | 2009-02-18 | 中国科学技术大学 | 5-羟甲基糠醛的制备方法 |
| KR20250091300A (ko) | 2008-12-09 | 2025-06-20 | 제넨테크, 인크. | 항-pd-l1 항체 및 t 세포 기능을 향상시키기 위한 그의 용도 |
| JP5844159B2 (ja) | 2009-02-09 | 2016-01-13 | ユニヴェルシテ デクス−マルセイユUniversite D’Aix−Marseille | Pd−1抗体およびpd−l1抗体ならびにその使用 |
| GB0903325D0 (en) | 2009-02-26 | 2009-04-08 | Univ Aberdeen | Antibody molecules |
| US20120135522A1 (en) | 2009-06-18 | 2012-05-31 | Kovach John S | Methods of modulating cell regulation by inhibiting p53 |
| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
| WO2011094683A2 (en) | 2010-01-29 | 2011-08-04 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Method of identifying myelodysplastic syndromes |
| MX2012012225A (es) | 2010-04-23 | 2013-08-27 | Piramal Entpr Ltd | Profármacos de agentes tearapéuticos de liberación de óxido nítrico. |
| US20140235649A1 (en) | 2011-05-24 | 2014-08-21 | Lixte Biotechnology, Inc. | Use of phosphatase inhibitors or histone deacetylase inhibitors to treat diseases characterized by loss of protein function |
| US9345705B2 (en) | 2011-09-15 | 2016-05-24 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
| WO2013056211A2 (en) | 2011-10-13 | 2013-04-18 | H. Lee Moffitt Cancer Center & Research Institute, Inc. | Telomerase reverse transcriptase deficience as diagnostic marker of myelodysplastic syndrome |
| NZ702237A (en) | 2012-06-01 | 2016-08-26 | Taisho Pharmaceutical Co Ltd | Prodrug of fluorine-containing amino acid |
| EP2867239A4 (en) * | 2012-06-29 | 2015-12-23 | Lixte Biotechnology Inc | OXABICYCLOHEPTANES AND OXABICYCLOHEPTENES FOR THE TREATMENT OF DIABETES |
| CN104619710B (zh) * | 2012-06-29 | 2017-09-22 | 里克思特生物技术有限公司 | 用于治疗再灌注损伤的氧杂二环庚烷和氧杂二环庚烯 |
| WO2014089279A1 (en) | 2012-12-05 | 2014-06-12 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Rnf41 as a biomarker predicting response to lenalidomide in non-del(5q) mds |
| EP2964026A4 (en) | 2013-03-05 | 2016-08-17 | Lixte Biotechnology Inc | HDAC INHIBITORS FOR THE TREATMENT OF TRAUMATIC BRAIN INJURY |
| WO2014149494A1 (en) | 2013-03-15 | 2014-09-25 | Lixte Biotechnology, Inc. | Sanguinarine analog pp2c inhibitors for cancer treatment |
| EA201591931A1 (ru) | 2013-04-09 | 2016-05-31 | Ликсте Байотекнолоджи, Инк. | Композиции оксабициклогептанов и оксабициклогептенов |
| JP2016538281A (ja) | 2013-11-15 | 2016-12-08 | リクスト・バイオテクノロジー,インコーポレイテッド | 血液脳関門を通過するタンパク質ホスファターゼ阻害剤 |
| US9051332B1 (en) | 2013-11-20 | 2015-06-09 | Transitions Optical, Inc. | Photochromic indeno-fused ring pyran compounds |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| EP3137083A2 (en) | 2014-04-28 | 2017-03-08 | Alembic Pharmaceuticals Limited | Novel polymorphic forms of vortioxetine and its pharmaceutically acceptable salts |
| WO2015196073A1 (en) | 2014-06-20 | 2015-12-23 | Lixte Biotechnology, Inc. | Oxabicycloheptanes and oxabicycloheptenes for the treatment of ovarian cancer |
| CN106572989B (zh) | 2014-07-24 | 2021-08-27 | H·李·莫菲特癌症中心与研究所公司 | 用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂 |
| EP3191096A4 (en) | 2014-09-12 | 2018-03-21 | Lixte Biotechnology, Inc. | Human dosing of phosphatase inhibitor |
| US9994584B2 (en) | 2014-10-15 | 2018-06-12 | Lixte Biotechnology, Inc. | Process of synthesizing 3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo[2.2.1] heptane-2-carboxylic acid |
| US9833450B2 (en) | 2015-02-19 | 2017-12-05 | Lixte Biotechnology, Inc. | Oxabicycloheptanes and oxabicycloheptenes for the treatment of depressive and stress disorders |
| SG11201708223QA (en) | 2015-04-17 | 2017-11-29 | Bristol Myers Squibb Co | Compositions comprising a combination of an anti-pd-1 antibody and another antibody |
| MX393461B (es) | 2015-05-15 | 2025-03-24 | Lixte Biotechnology Inc | Farmacos precursores de oxabicicloheptanos |
| JP7530702B2 (ja) | 2015-09-17 | 2024-08-08 | ノバルティス アーゲー | 有効性が増強されたcar t細胞療法 |
| US20190111053A1 (en) | 2016-01-27 | 2019-04-18 | Lixte Biotechnology, Inc. | Clinical regimen for treating myelodysplastic syndrome with phosphatase inhibitor |
| WO2017176289A1 (en) | 2016-04-08 | 2017-10-12 | Celgene Corporation | Uses of lenalidomide and car t-cells |
| ES2970913T3 (es) | 2016-12-08 | 2024-05-31 | Lixte Biotechnology Inc | Oxabicicloheptanos para modulación de la respuesta inmunitaria |
| WO2019113155A1 (en) | 2017-12-05 | 2019-06-13 | Lixte Biotechnology, Inc. | Oxabicycloheptanes for treatment of secondary acute myeloid leukemia |
| WO2019241536A1 (en) | 2018-06-14 | 2019-12-19 | Lixte Biotechnology, Inc. | Oxabicycloheptanes for enhancing car t cell function |
| RU201598U1 (ru) | 2020-05-14 | 2020-12-22 | Андрей Владимирович Дмитриев | Безреагентная испарительная градирня |
| JP2024504586A (ja) | 2021-01-19 | 2024-02-01 | リクスト・バイオテクノロジー,インコーポレイテッド | 小細胞肺がんの処置のためのオキサビシクロヘプタン |
| TW202342039A (zh) | 2022-01-04 | 2023-11-01 | 美商利克斯特生物科技公司 | 用於治療癌症或預防、抑制或降低癌症轉移風險之組成物及方法 |
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| US20250221985A1 (en) | 2025-07-10 |
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