ES2929576T3 - Combinaciones de inhibidores de histona deacetilasa 6 y el inhibidor de Her2 lapatinib para el uso en el tratamiento del cáncer de mama - Google Patents
Combinaciones de inhibidores de histona deacetilasa 6 y el inhibidor de Her2 lapatinib para el uso en el tratamiento del cáncer de mama Download PDFInfo
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- ES2929576T3 ES2929576T3 ES14851657T ES14851657T ES2929576T3 ES 2929576 T3 ES2929576 T3 ES 2929576T3 ES 14851657 T ES14851657 T ES 14851657T ES 14851657 T ES14851657 T ES 14851657T ES 2929576 T3 ES2929576 T3 ES 2929576T3
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| CN104926815B (zh) | 2008-01-04 | 2017-11-03 | 英特利凯恩有限责任公司 | 某些化学实体、组合物和方法 |
| PL2526093T3 (pl) * | 2010-01-22 | 2017-02-28 | Acetylon Pharmaceuticals, Inc. | Odwrócone związki amidowe jako inhibitory deacetylazy białkowej oraz sposoby ich stosowania |
| ES2568260T3 (es) | 2010-11-16 | 2016-04-28 | Acetylon Pharmaceuticals, Inc. | Compuestos de pirimidin hidroxi amida como inhibidores de proteína desacetilasa y métodos de uso de los mismos |
| AR084824A1 (es) | 2011-01-10 | 2013-06-26 | Intellikine Inc | Procesos para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| EP2839037B1 (en) | 2012-04-19 | 2018-12-26 | Acetylon Pharmaceuticals, Inc. | Biomarkers to identify patients that will respond to treatment and treating such patients |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| HRP20181367T4 (hr) | 2012-11-01 | 2021-11-26 | Infinity Pharmaceuticals, Inc. | Liječenje raka korištenjem modulatora izoforme pi3 kinaze |
| US9145412B2 (en) | 2012-11-02 | 2015-09-29 | Acetylon Pharmaceuticals, Inc. | Selective HDAC1 and HDAC2 inhibitors |
| JP6626437B2 (ja) * | 2013-10-08 | 2019-12-25 | アセチロン ファーマシューティカルズ インコーポレイテッドＡｃｅｔｙｌｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | ヒストンデアセチラーゼ阻害剤とＨｅｒ２阻害剤またはＰＩ３Ｋ阻害剤のいずれかの組み合わせ |
| ES2862126T3 (es) * | 2013-10-10 | 2021-10-07 | Acetylon Pharmaceuticals Inc | Compuestos de pirimidín-hidroxiamida como inhibidores de histona desacetilasa |
| JP6584391B2 (ja) * | 2013-10-10 | 2019-10-02 | アセチロン ファーマシューティカルズ インコーポレイテッドＡｃｅｔｙｌｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 非ホジキンリンパ腫を治療するための、ｈｄａｃ阻害剤単独またはｐｉ３ｋ阻害剤との組み合わせ |
| EP3060217B1 (en) | 2013-10-24 | 2022-06-08 | Mayo Foundation for Medical Education and Research | Treatment of polycystic diseases with an hdac6 inhibitor |
| US9949972B2 (en) | 2013-12-03 | 2018-04-24 | Acetylon Pharmaceuticals, Inc | Combinations of histone deacetylase inhibitors and immunomodulatory drugs |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| US9464073B2 (en) | 2014-02-26 | 2016-10-11 | Acetylon Pharmaceuticals, Inc. | Pyrimidine hydroxy amide compounds as HDAC6 selective inhibitors |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| CN107205988A (zh) | 2014-07-07 | 2017-09-26 | 埃斯泰隆制药公司 | 利用组蛋白脱乙酰酶抑制剂治疗白血病 |
| US9937174B2 (en) | 2014-12-05 | 2018-04-10 | University of Modena and Reggio Emilia | Combinations of histone deacetylase inhibitors and bendamustine |
| BR112017012504A2 (pt) | 2014-12-12 | 2018-01-09 | Acetylon Pharmaceuticals, Inc. | derivados de piperidina como inibidores de hdac1/2 |
| TW201718516A (zh) | 2015-06-08 | 2017-06-01 | 艾斯特隆製藥公司 | 組蛋白去乙醯酶抑制劑之晶形 |
| AU2016276573A1 (en) * | 2015-06-08 | 2018-01-04 | Acetylon Pharmaceuticals, Inc. | Methods of making protein deacetylase inhibitors |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514756D0 (en) * | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compound and method of use |
| WO2017184774A1 (en) * | 2016-04-19 | 2017-10-26 | Acetylon Pharmaceuticals, Inc. | Hdac inhibitors, alone or in combination with btk inhibitors, for treating chronic lymphocytic leukemia |
| WO2017214565A1 (en) | 2016-06-09 | 2017-12-14 | Dana-Farber Cancer Institute, Inc., | Methods of use and pharmaceutical combinations of hdac inhibitors with bet inhibitors |
| CA3028718A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| EP3496751B1 (en) | 2016-08-08 | 2022-10-19 | Acetylon Pharmaceuticals Inc. | Pharmaceutical combinations of histone deacetylase 6 inhibitors and cd20 inhibitory antibodies and uses thereof |
| JP7090611B2 (ja) | 2016-11-23 | 2022-06-24 | アセチロン ファーマシューティカルズ インコーポレイテッド | ヒストン脱アセチル化酵素阻害剤とプログラム細胞死リガンド１（ｐｄ－ｌ１）阻害剤とを含む医薬組み合わせ物及びその使用方法 |
| WO2018237007A1 (en) * | 2017-06-22 | 2018-12-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inhibitors of phosphoinositide 3-kinase and histone deacetylase for treatment of cancer |
| US20190216751A1 (en) * | 2017-11-15 | 2019-07-18 | California State University Northridge | Compositions and Methods for the Treatment and Prevention of Cancer |
| US11433069B2 (en) | 2017-12-01 | 2022-09-06 | University of Modena and Reggio Emilia | Methods of use and pharmaceutical combinations comprising histone deacetylase inhibitors and JAK1/2 inhibitors |
| MX2022000082A (es) * | 2019-06-21 | 2022-06-16 | Pattern Computer Inc | Composiciones terapeuticas y metodos para tratar canceres. |
Family Cites Families (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3549633A (en) | 1968-11-20 | 1970-12-22 | Merck & Co Inc | Process for preparation of 1-h-imidazo (4,5-b)pyrazin-2-ones |
| US6777217B1 (en) | 1996-03-26 | 2004-08-17 | President And Fellows Of Harvard College | Histone deacetylases, and uses related thereto |
| US20030129724A1 (en) | 2000-03-03 | 2003-07-10 | Grozinger Christina M. | Class II human histone deacetylases, and uses related thereto |
| DE60143520D1 (de) | 2000-03-24 | 2011-01-05 | Methylgene Inc | Inhibitoren der histon-deacetylase |
| JPWO2002074298A1 (ja) | 2001-03-21 | 2004-07-08 | 小野薬品工業株式会社 | Ｉｌ−６産生阻害剤 |
| US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
| DK1442019T3 (da) | 2001-11-01 | 2008-01-14 | Janssen Pharmaceutica Nv | Amidderivater som glycogensynthasekinase 3- beta-inhibitorer |
| HRP20040801A2 (en) | 2002-03-13 | 2005-04-30 | Janssen Pharmaceutica N.V. | Sulfonylamino derivatives as novel inhibitors of histone deacetylase |
| ATE425152T1 (de) | 2002-03-13 | 2009-03-15 | Janssen Pharmaceutica Nv | Aminocarbonylderivate als histone-deacetylase- inhibitoren |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| MY141521A (en) | 2002-12-12 | 2010-05-14 | Hoffmann La Roche | 5-substituted-six-membered heteroaromatic glucokinase activators |
| US7375228B2 (en) | 2003-03-17 | 2008-05-20 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| JP2006528603A (ja) | 2003-07-24 | 2006-12-21 | ビーエーエスエフ アクチェンゲゼルシャフト | ２−置換ピリミジン |
| PT1673349E (pt) | 2003-09-22 | 2010-09-28 | S Bio Pte Ltd | Derivados benzimidazole: preparação e aplicações farmacêuticas |
| US7868205B2 (en) | 2003-09-24 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| CA2561617A1 (en) | 2004-04-05 | 2005-10-20 | Aton Pharma, Inc. | Histone deacetylase inhibitor prodrugs |
| US20080182865A1 (en) | 2005-03-11 | 2008-07-31 | Witta Samir E | Histone deacetylase inhibitors sensitize cancer cells to epidermal growth factor inhibitors |
| AU2006226861B2 (en) | 2005-03-22 | 2012-08-16 | Dana-Farber Cancer Institute, Inc. | Treatment of protein degradation disorders |
| GB0510204D0 (en) | 2005-05-19 | 2005-06-22 | Chroma Therapeutics Ltd | Enzyme inhibitors |
| KR20080052611A (ko) | 2005-08-26 | 2008-06-11 | 메틸진 인크. | 히스톤 탈아세틸 효소의 벤조디아제핀 및 벤조피페라진유도체 억제제 |
| US7928253B2 (en) | 2005-11-01 | 2011-04-19 | Sumitomo Chemical Company, Limited | Method of producing 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one |
| ZA200806778B (en) | 2006-02-07 | 2009-11-25 | Astellas Pharma Inc | N-Hydroxyacrylamide compounds |
| JP5441416B2 (ja) | 2006-02-14 | 2014-03-12 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | 二官能性ヒストンデアセチラーゼインヒビター |
| WO2007130429A2 (en) | 2006-05-03 | 2007-11-15 | The President And Fellows Of Harvard College | Histone deacetylase and tubulin deacetylase inhibitors |
| WO2007144341A1 (en) | 2006-06-12 | 2007-12-21 | Vrije Universiteit Brussel | Differentiation of rat liver epithelial cells into hepatocyte-like cells |
| ES2288802B1 (es) | 2006-07-07 | 2008-12-16 | Universidad De Granada | Nuevos derivados de ftalimida como inhibidores de las histonas desacetilasas. |
| AU2007296743B2 (en) | 2006-09-11 | 2012-02-16 | Curis, Inc. | Tyrosine kinase inhibitors containing a zinc binding moiety |
| CN101573333B (zh) | 2006-10-28 | 2013-06-12 | 梅特希尔基因公司 | 组蛋白脱乙酰酶抑制剂 |
| AU2007334343A1 (en) * | 2006-12-15 | 2008-06-26 | Ordway Research Institute, Inc. | Treatments of therapy-resistant diseases comprising drug combinations |
| US8518979B2 (en) | 2007-02-21 | 2013-08-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Alpha-halo- and alpha-alkyl-cyclopropylcarboxy compounds and uses thereof |
| CN101951930A (zh) | 2008-02-19 | 2011-01-19 | 阿奈斯特药品株式会社 | 对身体功能的恢复有用的口服或经肠组合物 |
| US20110182888A1 (en) * | 2008-04-08 | 2011-07-28 | Peter Ordentlich | Administration of an Inhibitor of HDAC, an Inhibitor of HER-2, and a Selective Estrogen Receptor Modulator |
| US20110288070A1 (en) | 2008-05-05 | 2011-11-24 | ROGERS Kathryn | Methods for treating cognitive disorders using inhibitors of histone deacetylase |
| WO2009137503A1 (en) | 2008-05-05 | 2009-11-12 | Envivo Pharmaceuticals, Inc. | Hdac inhibitors and uses thereof |
| EP2303881A2 (en) | 2008-07-14 | 2011-04-06 | Gilead Sciences, Inc. | Fused heterocyclyc inhibitors of histone deacetylase and/or cyclin-dependent kinases |
| AU2009274549B2 (en) | 2008-07-23 | 2014-05-01 | Dana-Farber Cancer Institute, Inc. | Deacetylase inhibitors and uses thereof |
| EP2385832B1 (en) | 2009-01-08 | 2015-07-15 | Curis, Inc. | Phosphoinositide 3-kinase inhibitors with a zinc binding moiety |
| EP2429987A4 (en) | 2009-05-15 | 2012-10-03 | Korea Res Inst Chem Tech | AMIDE COMPOUND, PROCESS FOR PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME |
| CA2768466C (en) | 2009-07-22 | 2018-08-14 | The Board Of Trustees Of The University Of Illinois | Hdac inhibitors and therapeutic methods using the same |
| WO2011019393A2 (en) | 2009-08-11 | 2011-02-17 | President And Fellows Of Harvard College | Class- and isoform-specific hdac inhibitors and uses thereof |
| WO2011084991A2 (en) | 2010-01-08 | 2011-07-14 | President And Fellows Of Harvard College | Fluorinated hdac inhibitors and uses thereof |
| PL2526093T3 (pl) * | 2010-01-22 | 2017-02-28 | Acetylon Pharmaceuticals, Inc. | Odwrócone związki amidowe jako inhibitory deacetylazy białkowej oraz sposoby ich stosowania |
| JP2013525308A (ja) * | 2010-04-16 | 2013-06-20 | キュリス，インコーポレイテッド | Ｋ−ｒａｓ変異を有する癌の治療 |
| US8513421B2 (en) * | 2010-05-19 | 2013-08-20 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| EP2571352A4 (en) | 2010-05-21 | 2014-09-17 | Sloan Kettering Inst Cancer | SELECTIVE HDAC HEMMER |
| WO2012018499A2 (en) * | 2010-08-05 | 2012-02-09 | Acetylon Pharmaceuticals | Specific regulation of cytokine levels by hdac6 inhibitors |
| ES2568260T3 (es) * | 2010-11-16 | 2016-04-28 | Acetylon Pharmaceuticals, Inc. | Compuestos de pirimidin hidroxi amida como inhibidores de proteína desacetilasa y métodos de uso de los mismos |
| WO2012083243A1 (en) * | 2010-12-16 | 2012-06-21 | Massachusetts Institute Of Technology | Rnai based method of screening and characterizing drug combinations |
| EP2524918A1 (en) | 2011-05-19 | 2012-11-21 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyrazines derivates as kinase inhibitors |
| US9512083B2 (en) * | 2011-07-20 | 2016-12-06 | The General Hospital Corporation | Histone deacetylase 6 selective inhibitors for the treatment of bone disease |
| EP2839037B1 (en) | 2012-04-19 | 2018-12-26 | Acetylon Pharmaceuticals, Inc. | Biomarkers to identify patients that will respond to treatment and treating such patients |
| JP2015533173A (ja) | 2012-10-12 | 2015-11-19 | トラスティース・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | タンパク質脱アセチル化酵素阻害剤としてのピリミジンヒドロキシアミド化合物およびその使用方法 |
| HRP20181367T4 (hr) * | 2012-11-01 | 2021-11-26 | Infinity Pharmaceuticals, Inc. | Liječenje raka korištenjem modulatora izoforme pi3 kinaze |
| US9145412B2 (en) | 2012-11-02 | 2015-09-29 | Acetylon Pharmaceuticals, Inc. | Selective HDAC1 and HDAC2 inhibitors |
| US9139583B2 (en) | 2013-02-01 | 2015-09-22 | Acetylon Pharmaceuticals, Inc. | Selective HDAC3 inhibitors |
| EP2951153B1 (en) | 2013-02-01 | 2019-04-03 | Regenacy Pharmaceuticals, LLC | Selective hdac3 inhibitors |
| US20140357512A1 (en) | 2013-06-03 | 2014-12-04 | Acetylon Pharmaceuticals, Inc. | Histone deacetylase (hdac) biomarkers in multiple myeloma |
| JP6626437B2 (ja) * | 2013-10-08 | 2019-12-25 | アセチロン ファーマシューティカルズ インコーポレイテッドＡｃｅｔｙｌｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | ヒストンデアセチラーゼ阻害剤とＨｅｒ２阻害剤またはＰＩ３Ｋ阻害剤のいずれかの組み合わせ |
| ES2862126T3 (es) * | 2013-10-10 | 2021-10-07 | Acetylon Pharmaceuticals Inc | Compuestos de pirimidín-hidroxiamida como inhibidores de histona desacetilasa |
| JP6584391B2 (ja) * | 2013-10-10 | 2019-10-02 | アセチロン ファーマシューティカルズ インコーポレイテッドＡｃｅｔｙｌｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 非ホジキンリンパ腫を治療するための、ｈｄａｃ阻害剤単独またはｐｉ３ｋ阻害剤との組み合わせ |
| US20150105409A1 (en) * | 2013-10-10 | 2015-04-16 | Acetylon Pharmaceticals, Inc. | Hdac inhibitors, alone or in combination with btk inhibitors, for treating nonhodgkin's lymphoma |
| EA201690753A1 (ru) * | 2013-10-11 | 2016-07-29 | Эситайлон Фармасьютикалз, Инк. | Комбинации ингибиторов гистондеацетилазы и иммуномодулирующих лекарственных средств |
| EP3060217B1 (en) | 2013-10-24 | 2022-06-08 | Mayo Foundation for Medical Education and Research | Treatment of polycystic diseases with an hdac6 inhibitor |
| US9949972B2 (en) * | 2013-12-03 | 2018-04-24 | Acetylon Pharmaceuticals, Inc | Combinations of histone deacetylase inhibitors and immunomodulatory drugs |
| US20150176076A1 (en) * | 2013-12-20 | 2015-06-25 | Acetylon Pharmaceuticals, Inc. | Histone deacetylase 6 (hdac6) biomarkers in multiple myeloma |
| US9464073B2 (en) | 2014-02-26 | 2016-10-11 | Acetylon Pharmaceuticals, Inc. | Pyrimidine hydroxy amide compounds as HDAC6 selective inhibitors |
| US20150359794A1 (en) | 2014-06-13 | 2015-12-17 | Buck Institute For Research On Aging | Impairment of the large ribosomal subunit protein rpl24 by depletion or acetylation |
| CN107205988A (zh) * | 2014-07-07 | 2017-09-26 | 埃斯泰隆制药公司 | 利用组蛋白脱乙酰酶抑制剂治疗白血病 |
| US20160137630A1 (en) | 2014-10-08 | 2016-05-19 | Acetylon Pharmaceuticals, Inc. | Induction of gata2 by hdac1 and hdac2 inhibitors |
| WO2016090230A1 (en) | 2014-12-05 | 2016-06-09 | Acetylon Pharmaceuticals, Inc. | Pyrimidine hydroxy amide compounds for treating peripheral neuropathy |
| US9937174B2 (en) | 2014-12-05 | 2018-04-10 | University of Modena and Reggio Emilia | Combinations of histone deacetylase inhibitors and bendamustine |
| BR112017012504A2 (pt) | 2014-12-12 | 2018-01-09 | Acetylon Pharmaceuticals, Inc. | derivados de piperidina como inibidores de hdac1/2 |
| WO2017184774A1 (en) * | 2016-04-19 | 2017-10-26 | Acetylon Pharmaceuticals, Inc. | Hdac inhibitors, alone or in combination with btk inhibitors, for treating chronic lymphocytic leukemia |
-
2014
- 2014-10-06 JP JP2016521347A patent/JP6626437B2/ja active Active
- 2014-10-06 EP EP14851657.8A patent/EP3054952B1/en active Active
- 2014-10-06 US US14/506,889 patent/US9403779B2/en active Active
- 2014-10-06 WO PCT/US2014/059238 patent/WO2015054099A1/en not_active Ceased
- 2014-10-06 ES ES14851657T patent/ES2929576T3/es active Active
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2016
- 2016-06-22 US US15/189,554 patent/US10722512B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2015054099A1 (en) | 2015-04-16 |
| JP2016536286A (ja) | 2016-11-24 |
| US20170020872A1 (en) | 2017-01-26 |
| US20150099744A1 (en) | 2015-04-09 |
| EP3054952A1 (en) | 2016-08-17 |
| EP3054952B1 (en) | 2022-10-26 |
| US10722512B2 (en) | 2020-07-28 |
| JP6626437B2 (ja) | 2019-12-25 |
| US9403779B2 (en) | 2016-08-02 |
| EP3054952A4 (en) | 2017-04-12 |
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