CA2776944A1 - Combinations of a pi3k inhibitor and a mek inhibitor - Google Patents
Combinations of a pi3k inhibitor and a mek inhibitor Download PDFInfo
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- CA2776944A1 CA2776944A1 CA2776944A CA2776944A CA2776944A1 CA 2776944 A1 CA2776944 A1 CA 2776944A1 CA 2776944 A CA2776944 A CA 2776944A CA 2776944 A CA2776944 A CA 2776944A CA 2776944 A1 CA2776944 A1 CA 2776944A1
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| US25085209P | 2009-10-12 | 2009-10-12 | |
| US61/250,852 | 2009-10-12 | ||
| PCT/EP2010/065149 WO2011054620A1 (en) | 2009-10-12 | 2010-10-11 | Combinations of a pi3k inhibitor and a mek inhibitor |
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| CA2776944A1 true CA2776944A1 (en) | 2011-05-12 |
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| CA2776944A Abandoned CA2776944A1 (en) | 2009-10-12 | 2010-10-11 | Combinations of a pi3k inhibitor and a mek inhibitor |
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|---|---|---|---|---|
| MX2011000440A (es) | 2008-07-11 | 2011-02-24 | Novartis Ag | Combinacion de (a) un inhibidor de fosfoinositido 3-cinasa y (b) un modulador de la ruta de ras/raf/mek. |
| EA024252B1 (ru) | 2009-01-08 | 2016-08-31 | Кьюрис, Инк. | Ингибиторы фосфоинозитид-3-киназ с цинксвязывающей группой |
| PH12012501361A1 (en) | 2009-12-31 | 2012-10-22 | Centro Nac De Investigaciones Oncologicas Cnio | Tricyclic compounds for use as kinase inhibitors |
| WO2012098387A1 (en) | 2011-01-18 | 2012-07-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | 6, 7-ring-fused triazolo [4, 3 - b] pyridazine derivatives as pim inhibitors |
| CA2830822C (en) | 2011-04-01 | 2018-10-02 | Curis, Inc. | A thienopyrimidine phosphoinositide 3-kinase inhibitor with a zinc binding moiety |
| AR087405A1 (es) | 2011-08-01 | 2014-03-19 | Genentech Inc | Metodos para tratar el cancer por el uso de antagonistas de union al eje pd-1 e inhibidores de mek |
| US9675595B2 (en) | 2011-08-31 | 2017-06-13 | Novartis Ag | Synergistic combinations of PI3K- and MEK-inhibitors |
| CN103957902A (zh) | 2011-10-13 | 2014-07-30 | 基因泰克公司 | 药理学诱导的胃酸过少的治疗 |
| EP2776051A4 (en) * | 2011-10-28 | 2015-06-17 | Hoffmann La Roche | THERAPEUTIC COMBINATIONS AND METHOD FOR THE TREATMENT OF MELANOMA |
| WO2013082511A1 (en) | 2011-12-02 | 2013-06-06 | Genentech, Inc. | Methods for overcoming tumor resistance to vegf antagonists |
| PE20142020A1 (es) * | 2012-04-06 | 2014-12-24 | Sanofi Sa | Metodos para tratar el cancer usando inhibidor de pi3k e inhibidor de mek |
| JP6093757B2 (ja) * | 2012-04-19 | 2017-03-08 | 国立大学法人九州大学 | 医薬組成物 |
| US9107926B2 (en) | 2012-06-08 | 2015-08-18 | Genentech, Inc. | Mutant selectivity and combinations of a phosphoinositide 3-kinase inhibitor compound and chemotherapeutic agents for the treatment of cancer |
| EP2879708A4 (en) | 2012-08-02 | 2016-03-16 | Genentech Inc | ANTIBODY AND ANTI-ETBR IMMUNOCONJUGATES |
| US9463251B2 (en) | 2012-08-02 | 2016-10-11 | Genentech, Inc. | Anti-ETBR antibodies and immunoconjugates |
| RS59113B1 (sr) * | 2012-08-17 | 2019-09-30 | Hoffmann La Roche | Kombinovane terapije za melanom koje uključuju davanje kobimetiniba i vemurafiniba |
| SG11201507477XA (en) * | 2013-03-14 | 2015-10-29 | Genentech Inc | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
| US9532987B2 (en) | 2013-09-05 | 2017-01-03 | Genentech, Inc. | Use of a combination of a MEK inhibitor and an ERK inhibitor for treatment of hyperproliferative diseases |
| ES2779975T3 (es) | 2014-02-07 | 2020-08-21 | Verastem Inc | Métodos y composiciones para tratar el crecimiento celular anormal |
| SG10202007111TA (en) | 2014-07-15 | 2020-09-29 | Genentech Inc | Compositions for treating cancer using pd-1 axis binding antagonists and mek inhibitors |
| WO2016040806A1 (en) * | 2014-09-11 | 2016-03-17 | The Regents Of The University Of California | mTORC1 INHIBITORS |
| ES3014591T3 (en) | 2018-09-11 | 2025-04-23 | Curis Inc | Combination therapy with a phosphoinositide 3-kinase inhibitor with a zinc binding moiety |
| CN110420330B (zh) * | 2019-07-19 | 2020-05-29 | 南京医科大学 | 一种pi3k与mth1靶向药组合物的制药用途 |
| JP2022547358A (ja) | 2019-09-13 | 2022-11-14 | ジ インスティテュート オブ キャンサー リサーチ：ロイヤル キャンサー ホスピタル | 治療組成物、組み合わせ、及び使用方法 |
| US11873296B2 (en) | 2022-06-07 | 2024-01-16 | Verastem, Inc. | Solid forms of a dual RAF/MEK inhibitor |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1470356A1 (de) * | 1964-01-15 | 1970-04-30 | Thomae Gmbh Dr K | Neue Thieno[3,2-d]pyrimidine und Verfahren zu ihrer Herstellung |
| BE754606A (fr) * | 1969-08-08 | 1971-02-08 | Thomae Gmbh Dr K | Nouvelles 2-aminoalcoylamino-thieno(3,2-d)pyrimidines et leurs procedesde fabrication |
| BE759493A (fr) * | 1969-11-26 | 1971-05-25 | Thomae Gmbh Dr K | Nouvelles 2-(5-nitro-2-furyl)-thieno(3,2-d) pyrimidines et procedes pour les fabriquer |
| US3763156A (en) * | 1970-01-28 | 1973-10-02 | Boehringer Sohn Ingelheim | 2-heterocyclic amino-4-morpholinothieno(3,2-d)pyrimidines |
| CH592668A5 (enExample) * | 1973-10-02 | 1977-10-31 | Delalande Sa | |
| GB1570494A (en) * | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| US4510139A (en) * | 1984-01-06 | 1985-04-09 | Sterling Drug Inc. | Substituted aminobenzamides and their use as agents which inhibit lipoxygenase activity |
| WO1995026956A1 (en) * | 1994-04-01 | 1995-10-12 | Shionogi & Co., Ltd. | Oxime derivative and bactericide containing the same as active ingredient |
| US6974878B2 (en) * | 2001-03-21 | 2005-12-13 | Symyx Technologies, Inc. | Catalyst ligands, catalytic metal complexes and processes using same |
| US6608053B2 (en) * | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| US7498304B2 (en) * | 2000-06-16 | 2009-03-03 | Curis, Inc. | Angiogenesis-modulating compositions and uses |
| EE05450B1 (et) * | 2000-07-19 | 2011-08-15 | Warner-Lambert Company | 4-jodofenlaminobenshdroksaamhapete oksgeenitud estrid, nende kristallvormid ja farmatseutilised kompositsioonid ning kasutamine |
| US7235537B2 (en) * | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| EP1606283B1 (en) * | 2003-03-03 | 2008-10-08 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
| US20050049276A1 (en) * | 2003-07-23 | 2005-03-03 | Warner-Lambert Company, Llc | Imidazopyridines and triazolopyridines |
| US7538120B2 (en) * | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| EP1674452A4 (en) * | 2003-09-19 | 2007-10-10 | Chugai Pharmaceutical Co Ltd | NOVEL 4-PHENYLAMINO-BENZALDOXIME DERIVATIVE AND ITS USE AS MEK INHIBITOR |
| US7517994B2 (en) * | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| GB0423653D0 (en) | 2004-10-25 | 2004-11-24 | Piramed Ltd | Pharmaceutical compounds |
| HRP20110498T1 (hr) * | 2005-10-07 | 2011-08-31 | Exelixis | Azetidini kao inhibitori mek za liječenje proliferativnih bolesti |
| BRPI0710874A2 (pt) * | 2006-04-26 | 2012-02-14 | Hoffmann La Roche | compostos de tienopirimidina, processos de produção dos referidos compostos, composições farmacêuticas contendo os mesmos, kit, produto, e usos dos compostos |
| WO2008021389A2 (en) * | 2006-08-16 | 2008-02-21 | Exelixis, Inc. | Using pi3k and mek modulators in treatments of cancer |
| AU2007329352B2 (en) * | 2006-12-07 | 2013-01-17 | F. Hoffmann-La Roche Ag | Phosphoinositide 3-kinase inhibitor compounds and methods of use |
| EP2205242B1 (en) * | 2007-09-12 | 2015-04-15 | Genentech, Inc. | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use |
| CN103841976A (zh) * | 2011-04-01 | 2014-06-04 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
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- 2010-10-11 JP JP2012533589A patent/JP2013507415A/ja not_active Ceased
- 2010-10-11 AU AU2010314287A patent/AU2010314287A1/en not_active Abandoned
- 2010-10-11 TW TW099134615A patent/TWI428336B/zh not_active IP Right Cessation
- 2010-10-11 EP EP10768448.2A patent/EP2488178B1/en not_active Not-in-force
- 2010-10-11 PE PE2012000470A patent/PE20121816A1/es not_active Application Discontinuation
- 2010-10-11 US US12/902,062 patent/US20110086837A1/en not_active Abandoned
- 2010-10-11 NZ NZ599939A patent/NZ599939A/en not_active IP Right Cessation
- 2010-10-11 WO PCT/EP2010/065149 patent/WO2011054620A1/en not_active Ceased
- 2010-10-11 RU RU2012118974/15A patent/RU2563193C2/ru not_active IP Right Cessation
- 2010-10-11 BR BR112012008483A patent/BR112012008483A2/pt not_active IP Right Cessation
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- 2010-10-11 ES ES10768448.2T patent/ES2609767T3/es active Active
- 2010-10-11 MA MA34821A patent/MA33974B1/fr unknown
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| CO6531463A2 (es) | 2012-09-28 |
| US20110086837A1 (en) | 2011-04-14 |
| CR20120173A (es) | 2012-07-04 |
| WO2011054620A1 (en) | 2011-05-12 |
| HK1175125A1 (en) | 2013-06-28 |
| EP2488178A1 (en) | 2012-08-22 |
| PE20121816A1 (es) | 2013-01-02 |
| AU2010314287A1 (en) | 2012-05-03 |
| JP2015038110A (ja) | 2015-02-26 |
| RU2012118974A (ru) | 2013-11-20 |
| NZ599939A (en) | 2014-02-28 |
| IL219105A0 (en) | 2012-06-28 |
| CL2012000913A1 (es) | 2012-09-14 |
| CN102740851B (zh) | 2013-12-18 |
| ES2609767T3 (es) | 2017-04-24 |
| PH12012500709A1 (en) | 2012-10-29 |
| KR101489045B1 (ko) | 2015-02-02 |
| JP2013507415A (ja) | 2013-03-04 |
| AU2010314287A2 (en) | 2012-07-12 |
| TWI428336B (zh) | 2014-03-01 |
| JP5745678B2 (ja) | 2015-07-08 |
| EP2488178B1 (en) | 2016-11-16 |
| MX345155B (es) | 2017-01-18 |
| AR078588A1 (es) | 2011-11-16 |
| BR112012008483A2 (pt) | 2019-09-24 |
| ZA201202618B (en) | 2014-10-29 |
| ECSP12011865A (es) | 2012-06-29 |
| MX2012004286A (es) | 2012-05-22 |
| RU2563193C2 (ru) | 2015-09-20 |
| CN102740851A (zh) | 2012-10-17 |
| MA33974B1 (fr) | 2013-02-01 |
| TW201118082A (en) | 2011-06-01 |
| KR20120064132A (ko) | 2012-06-18 |
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