JP6728072B2 - ｍｄｍ２阻害剤の間欠投与 - Google Patents
ｍｄｍ２阻害剤の間欠投与 Download PDFInfo
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- JP6728072B2 JP6728072B2 JP2016574274A JP2016574274A JP6728072B2 JP 6728072 B2 JP6728072 B2 JP 6728072B2 JP 2016574274 A JP2016574274 A JP 2016574274A JP 2016574274 A JP2016574274 A JP 2016574274A JP 6728072 B2 JP6728072 B2 JP 6728072B2
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| KR20180058866A (ko) | 2010-08-13 | 2018-06-01 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| BR112014009418A2 (pt) | 2011-10-18 | 2017-04-18 | Aileron Therapeutics Inc | macrociclos peptidomiméticos |
| MX2015005244A (es) | 2012-11-01 | 2015-07-14 | Aileron Therapeutics Inc | Aminoacidos disustituidos y metodos de preparacion y el uso de los mismos. |
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| AU2015320549A1 (en) | 2014-09-24 | 2017-04-13 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| AU2015320545C1 (en) | 2014-09-24 | 2020-05-14 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| SG11201707750YA (en) | 2015-03-20 | 2017-10-30 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| CN109982702A (zh) * | 2016-11-15 | 2019-07-05 | 诺华股份有限公司 | HDM2-p53相互作用抑制剂的剂量及方案 |
| RU2753527C2 (ru) * | 2017-03-31 | 2021-08-17 | Новартис Аг | ДОЗА И СХЕМА ВВЕДЕНИЯ ИНГИБИТОРА ВЗАИМОДЕЙСТВИЯ HDM2 С p53 ПРИ ГЕМАТОЛОГИЧЕСКИХ ОПУХОЛЯХ |
| WO2019174576A1 (zh) * | 2018-03-12 | 2019-09-19 | 罗欣药业(上海)有限公司 | 咪唑并吡咯酮化合物及其应用 |
| EP3768717A1 (en) | 2018-03-20 | 2021-01-27 | Novartis AG | Pharmaceutical combinations |
| IL319432A (en) * | 2018-04-30 | 2025-05-01 | Kartos Therapeutics Inc | Methods of treating cancer |
| JP2021525795A (ja) * | 2018-05-25 | 2021-09-27 | カルトス セラピューティクス，インコーポレイテッド | 骨髄増殖性腫瘍を治療する方法 |
| WO2020128892A1 (en) * | 2018-12-20 | 2020-06-25 | Novartis Ag | Extended low dose regimens for mdm2 inhibitors |
| JP2022547311A (ja) | 2019-09-16 | 2022-11-11 | ノバルティス アーゲー | 骨髄線維症の治療のためのｍｄｍ２阻害剤の使用 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9721069D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Polymeric derivatives of camptothecin |
| US6548531B2 (en) | 2001-02-09 | 2003-04-15 | Hoffmann-La Roche Inc. | Method for cancer therapy |
| US20030139373A1 (en) | 2001-11-20 | 2003-07-24 | Breimer Lars Holger | Method for cancer therapy |
| AU2006216780B8 (en) | 2005-02-22 | 2010-04-22 | The Regents Of The University Of Michigan | Small molecule inhibitors of MDM2 and uses thereof |
| CN102770182B (zh) * | 2009-12-22 | 2014-10-29 | 诺华股份有限公司 | 被取代的异喹啉酮类和喹唑酮类 |
| US8440693B2 (en) * | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| PL2361667T3 (pl) | 2010-02-25 | 2015-07-31 | General Electric Technology Gmbh | Płuczka wodna i sposób oczyszczania gazu procesowego |
| CA2817585A1 (en) * | 2010-11-12 | 2012-05-18 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
| WO2012080389A1 (en) * | 2010-12-16 | 2012-06-21 | Roche Glycart Ag | Combination therapy of an afucosylated cd20 antibody with a mdm2 inhibitor |
| BR112014003113A2 (pt) | 2011-08-11 | 2017-03-14 | Estetra Sprl | método de contracepção de emergência em uma fêmea mamífero |
| EP2793890B1 (en) | 2011-12-21 | 2016-09-07 | Merck Sharp & Dohme Corp. | Substituted piperidines as hdm2 inhibitors |
| US8815926B2 (en) | 2012-01-26 | 2014-08-26 | Novartis Ag | Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases |
| US9216170B2 (en) * | 2012-03-19 | 2015-12-22 | Hoffmann-La Roche Inc. | Combination therapy for proliferative disorders |
| US20130245089A1 (en) | 2012-03-19 | 2013-09-19 | Hoffmann-La Roche Inc. | Method for administration |
| US20150159222A1 (en) | 2012-07-31 | 2015-06-11 | Novartis Ag | Markers associated with human double minute 2 inhibitors |
| US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
| US9556180B2 (en) | 2013-01-22 | 2017-01-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction |
| EA201690785A1 (ru) | 2013-12-05 | 2016-10-31 | Ф. Хоффманн-Ля Рош Аг | Новая комбинированная терапия острого миелоидного лейкоза (омл) |
| US20160331751A1 (en) | 2013-12-23 | 2016-11-17 | Novartis Ag | Pharmaceutical compositions |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| TW201613576A (en) | 2014-06-26 | 2016-04-16 | Novartis Ag | Intermittent dosing of MDM2 inhibitor |
| EP3253387A4 (en) | 2015-02-06 | 2018-12-19 | Unity Biotechnology, Inc. | Compounds and uses in treatment of senescence-associated conditons |
| WO2016167236A1 (ja) | 2015-04-13 | 2016-10-20 | 第一三共株式会社 | Ｍｄｍ２阻害剤とｂｔｋ阻害剤との併用治療法 |
| TWI750129B (zh) | 2015-08-03 | 2021-12-21 | 瑞士商諾華公司 | 作為血液學毒性生物標記之ｇｄｆ-１５ |
| CN108348520A (zh) | 2015-08-28 | 2018-07-31 | 诺华股份有限公司 | Mdm2抑制剂和其组合 |
| CN109982702A (zh) | 2016-11-15 | 2019-07-05 | 诺华股份有限公司 | HDM2-p53相互作用抑制剂的剂量及方案 |
| AU2017364332B2 (en) | 2016-11-22 | 2020-07-09 | Novartis Ag | Chemical process for preparing imidazopyrrolidinone derivatives and intermediates thereof |
| WO2018158225A1 (en) | 2017-02-28 | 2018-09-07 | Les Laboratoires Servier | Combination of a bcl-2 inhibitor and a mdm2 inhibitor, uses and pharmaceutical compositions thereof |
| RU2753527C2 (ru) | 2017-03-31 | 2021-08-17 | Новартис Аг | ДОЗА И СХЕМА ВВЕДЕНИЯ ИНГИБИТОРА ВЗАИМОДЕЙСТВИЯ HDM2 С p53 ПРИ ГЕМАТОЛОГИЧЕСКИХ ОПУХОЛЯХ |
| CN111163781B (zh) | 2017-10-12 | 2023-05-16 | 诺华股份有限公司 | 用于治疗癌症的mdm2抑制剂与erk抑制剂的组合 |
| EP3768717A1 (en) | 2018-03-20 | 2021-01-27 | Novartis AG | Pharmaceutical combinations |
| WO2020092221A1 (en) | 2018-10-30 | 2020-05-07 | Dana-Farber Cancer Institute, Inc. | Method of treatment of p53 wt tumors |
| WO2020128892A1 (en) | 2018-12-20 | 2020-06-25 | Novartis Ag | Extended low dose regimens for mdm2 inhibitors |
| JP2022525734A (ja) | 2019-04-04 | 2022-05-19 | ノバルティス アーゲー | シレマドリンスクシナート |
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