KR20170044097A - 히스톤 탈아세틸화효소 저해제에 의한 백혈병의 치료 - Google Patents
히스톤 탈아세틸화효소 저해제에 의한 백혈병의 치료 Download PDFInfo
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- KR20170044097A KR20170044097A KR1020177003321A KR20177003321A KR20170044097A KR 20170044097 A KR20170044097 A KR 20170044097A KR 1020177003321 A KR1020177003321 A KR 1020177003321A KR 20177003321 A KR20177003321 A KR 20177003321A KR 20170044097 A KR20170044097 A KR 20170044097A
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Family Cites Families (66)
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|---|---|---|---|---|
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| 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 |
| US7288567B2 (en) | 2000-03-24 | 2007-10-30 | Methylgene Inc. | Inhibitors of histone deacetylase |
| WO2002074298A1 (en) | 2001-03-21 | 2002-09-26 | Ono Pharmaceutical Co., Ltd. | Il-6 production inhibitors |
| US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
| HUP0402330A3 (en) | 2001-11-01 | 2010-03-29 | Janssen Pharmaceutica Nv | Amide derivatives as glycogen synthase kinase 3-beta inhibitors, process for producing them, pharmaceutical compositions containing them and use thereof |
| US7501417B2 (en) | 2002-03-13 | 2009-03-10 | Janssen Pharmaceutica, N.V. | Aminocarbonyl-derivatives as novel inhibitors of histone deacetylase |
| OA12793A (en) | 2002-03-13 | 2006-07-10 | Janssen Pharmaceutica Nv | Sulfonylamino-derivatives as novel inhibitors of histone deacetylase. |
| TWI319387B (en) | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| PE20040801A1 (es) | 2002-12-12 | 2004-11-25 | Hoffmann La Roche | Derivados de pirazina y piridina 5-sustituidos como activadores de glucoquinasa |
| US7244751B2 (en) | 2003-02-14 | 2007-07-17 | Shenzhen Chipscreen Biosciences Ltd. | Histone deacetylase inhibitors of novel benzamide derivatives with potent differentiation and anti-proliferation activity |
| EP1608628A2 (en) | 2003-03-17 | 2005-12-28 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| DK1651618T3 (da) | 2003-07-24 | 2007-05-14 | Basf Ag | 2-substituerede pyrimidiner |
| US7781595B2 (en) | 2003-09-22 | 2010-08-24 | S*Bio Pte Ltd. | Benzimidazole derivatives: preparation and pharmaceutical applications |
| EP1663953A1 (en) | 2003-09-24 | 2006-06-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| WO2005097747A1 (en) | 2004-04-05 | 2005-10-20 | Aton Pharma, Inc. | Histone deacetylase inhibitor prodrugs |
| US8999289B2 (en) | 2005-03-22 | 2015-04-07 | President And Fellows Of Harvard College | Treatment of protein degradation disorders |
| GB0510204D0 (en) | 2005-05-19 | 2005-06-22 | Chroma Therapeutics Ltd | Enzyme inhibitors |
| AU2006284403A1 (en) | 2005-08-26 | 2007-03-01 | Methylgene Inc. | Benzodiazepine and benzopiperazine analog inhibitors of histone deacetylase |
| WO2007052383A1 (ja) | 2005-11-01 | 2007-05-10 | Sumitomo Chemical Company, Limited | ６，６−ジメチル−３−オキサビシクロ［３．１．０］ヘキサン−２−オンの製造方法 |
| AU2007213018A1 (en) | 2006-02-07 | 2007-08-16 | Astellas Pharma Inc. | N-hydroxyacrylamide compounds |
| US8222423B2 (en) | 2006-02-14 | 2012-07-17 | Dana-Farber Cancer Institute, Inc. | Bifunctional histone deacetylase inhibitors |
| CN101466670B (zh) | 2006-04-07 | 2013-04-17 | 梅特希尔基因公司 | 组蛋白脱乙酰酶抑制剂 |
| AU2007243519A1 (en) | 2006-04-26 | 2007-11-08 | Merck Sharp & Dohme Corp. | Disubstituted aniline compounds |
| AU2007248656B2 (en) | 2006-05-03 | 2013-04-04 | Dana-Farber Cancer Institute, Inc. | Histone deacetylase and tubulin deacetylase inhibitors |
| US20100278782A1 (en) | 2006-06-12 | 2010-11-04 | 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. |
| WO2008033746A2 (en) | 2006-09-11 | 2008-03-20 | Curis, Inc. | Tyrosine kinase inhibitors containing a zinc binding moiety |
| PL2343286T3 (pl) | 2006-10-28 | 2015-06-30 | Methylgene Inc | Pochodne dibenzo[b,f][1,4]oksazepiny jako inhibitory deacetylazy histonowej |
| CA2668070A1 (en) | 2006-10-30 | 2008-05-08 | Chroma Therapeutics Ltd. | Hydroxamates as inhibitors of histone deacetylase |
| WO2008102348A1 (en) | 2007-02-21 | 2008-08-28 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Alpha-halo- and alpha-alkyl-cyclopropylcarboxy compounds and uses thereof |
| JP2010120852A (ja) | 2007-03-09 | 2010-06-03 | Daiichi Sankyo Co Ltd | 新規なジアミド誘導体 |
| TW200924777A (en) | 2007-09-14 | 2009-06-16 | Methylgene Inc | Combination therapy |
| US8778410B2 (en) | 2008-02-19 | 2014-07-15 | Earnest Medicine Co., Ltd. | Oral or enteral composition useful for recovery of physical functions |
| 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 |
| NZ590320A (en) | 2008-07-14 | 2012-12-21 | Gilead Sciences Inc | Fused heterocyclyc inhibitors of histone deacetylase and/or cyclin-dependent kinases |
| KR101708946B1 (ko) | 2008-07-23 | 2017-02-21 | 다나-파버 캔서 인스티튜트 인크. | 탈아세틸화제 억제제 및 그것의 용도 |
| DK2385832T3 (en) | 2009-01-08 | 2015-09-21 | Curis Inc | Phosphoinositid-3-kinase-inhibitorer med en zink-bindingsdel |
| 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 |
| US8431538B2 (en) | 2009-07-22 | 2013-04-30 | The Board Of Trustees Of The University Of Illinois | HDAC inhibitors and therapeutic methods of using same |
| WO2011019393A2 (en) | 2009-08-11 | 2011-02-17 | President And Fellows Of Harvard College | Class- and isoform-specific hdac inhibitors and uses thereof |
| US20130040998A1 (en) | 2010-01-08 | 2013-02-14 | Dana-Farber Cancer Institute, Inc. | Fluorinated hdac inhibitors and uses thereof |
| CN102933558B (zh) | 2010-01-22 | 2016-03-16 | 埃斯泰隆制药公司 | 作为蛋白质去乙酰化酶抑制剂的反向酰胺化合物及其使用方法 |
| CA2800143A1 (en) | 2010-05-21 | 2011-11-24 | The Trustees Of Columbia University In The City Of New York | Selective hdac inhibitors |
| WO2012018499A2 (en) | 2010-08-05 | 2012-02-09 | Acetylon Pharmaceuticals | Specific regulation of cytokine levels by hdac6 inhibitors |
| US8859502B2 (en) | 2010-09-13 | 2014-10-14 | Celgene Corporation | Therapy for MLL-rearranged leukemia |
| EP3067346A1 (en) | 2010-11-16 | 2016-09-14 | Acetylon Pharmaceuticals, Inc. | Pyrimidine hydroxy amide compounds as protein deacetylase inhibitors and methods of use thereof |
| US8404738B2 (en) | 2011-01-21 | 2013-03-26 | Hoffmann-La Roche Inc. | 4-amino-N-hydroxy-benzamides for the treatment of cancer |
| EP2524918A1 (en) | 2011-05-19 | 2012-11-21 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyrazines derivates as kinase inhibitors |
| WO2013013113A2 (en) * | 2011-07-20 | 2013-01-24 | The General Hospital Corporation | Histone deacetylase 6 selective inhibitors for the treatment of bone disease |
| HK1207403A1 (en) | 2012-04-19 | 2016-01-29 | Acetylon Pharmaceuticals, Inc. | Biomarkers to identify patients that will respond to treatment and treating such patients |
| 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 |
| US9096549B2 (en) | 2013-02-01 | 2015-08-04 | Acetylon Pharmaceuticals, Inc. | Selective HDAC3 inhibitors |
| JP2016523236A (ja) | 2013-06-03 | 2016-08-08 | 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． | 多発性骨髄腫におけるヒストン脱アセチル化酵素（ｈｄａｃ）バイオマーカー |
| ES2929576T3 (es) | 2013-10-08 | 2022-11-30 | Acetylon Pharmaceuticals Inc | Combinaciones de inhibidores de histona deacetilasa 6 y el inhibidor de Her2 lapatinib para el uso en el tratamiento del cáncer de mama |
| ES2818933T3 (es) | 2013-10-10 | 2021-04-14 | Acetylon Pharmaceuticals Inc | Inhibidores de la HDAC en combinación con los inhibidores de la pi3k, para el tratamiento del linfoma no Hodgkin |
| ES2862126T3 (es) | 2013-10-10 | 2021-10-07 | Acetylon Pharmaceuticals Inc | Compuestos de pirimidín-hidroxiamida como inhibidores de histona desacetilasa |
| JP2016536354A (ja) | 2013-10-10 | 2016-11-24 | 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ｂｔｋ阻害剤との組み合わせ |
| WO2015054175A1 (en) | 2013-10-11 | 2015-04-16 | Acetylon Pharmaceuticals, Inc. | Combinations of histone deactylase inhibitors and immunomodulatory drugs |
| MX2016007251A (es) | 2013-12-03 | 2016-09-07 | Acetylon Pharmaceuticals Inc | Combinaciones de inhibidores de histona deacetilasa y farmacos inmunomoduladores. |
| ES2936812T3 (es) | 2013-12-20 | 2023-03-22 | Acetylon Pharmaceuticals Inc | Biomarcadores de histona desacetilasa 6 (HDAC6) en mieloma múltiple |
| US9464073B2 (en) | 2014-02-26 | 2016-10-11 | Acetylon Pharmaceuticals, Inc. | Pyrimidine hydroxy amide compounds as HDAC6 selective inhibitors |
-
2015
- 2015-07-06 EA EA201790142A patent/EA201790142A1/ru unknown
- 2015-07-06 JP JP2017522324A patent/JP6952602B2/ja active Active
- 2015-07-06 BR BR112017000301A patent/BR112017000301A2/pt not_active Application Discontinuation
- 2015-07-06 US US14/792,046 patent/US9833466B2/en active Active
- 2015-07-06 CN CN201580047830.2A patent/CN107205988A/zh active Pending
- 2015-07-06 EP EP15818585.0A patent/EP3166603B1/en active Active
- 2015-07-06 MX MX2017000307A patent/MX2017000307A/es unknown
- 2015-07-06 AU AU2015288060A patent/AU2015288060A1/en not_active Abandoned
- 2015-07-06 WO PCT/US2015/039225 patent/WO2016007423A1/en not_active Ceased
- 2015-07-06 KR KR1020177003321A patent/KR20170044097A/ko not_active Withdrawn
- 2015-07-06 SG SG11201700094TA patent/SG11201700094TA/en unknown
- 2015-07-06 CA CA2954522A patent/CA2954522A1/en not_active Abandoned
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2017
- 2017-01-05 IL IL249935A patent/IL249935A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2954522A1 (en) | 2016-01-14 |
| JP2017524735A (ja) | 2017-08-31 |
| EA201790142A1 (ru) | 2017-07-31 |
| IL249935A0 (en) | 2017-03-30 |
| WO2016007423A1 (en) | 2016-01-14 |
| US20160030458A1 (en) | 2016-02-04 |
| CN107205988A (zh) | 2017-09-26 |
| EP3166603A4 (en) | 2017-12-13 |
| US9833466B2 (en) | 2017-12-05 |
| AU2015288060A1 (en) | 2017-02-09 |
| EP3166603A1 (en) | 2017-05-17 |
| EP3166603B1 (en) | 2020-02-12 |
| JP6952602B2 (ja) | 2021-10-20 |
| SG11201700094TA (en) | 2017-02-27 |
| BR112017000301A2 (pt) | 2017-11-07 |
| MX2017000307A (es) | 2017-11-23 |
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