RU2727802C2 - Апилимод для применения в лечении рака почек - Google Patents
Апилимод для применения в лечении рака почек Download PDFInfo
- Publication number
- RU2727802C2 RU2727802C2 RU2017119065A RU2017119065A RU2727802C2 RU 2727802 C2 RU2727802 C2 RU 2727802C2 RU 2017119065 A RU2017119065 A RU 2017119065A RU 2017119065 A RU2017119065 A RU 2017119065A RU 2727802 C2 RU2727802 C2 RU 2727802C2
- Authority
- RU
- Russia
- Prior art keywords
- apilimod
- use according
- inhibitor
- cancer
- pharmaceutically acceptable
- Prior art date
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| AU2015209133B2 (en) | 2014-01-24 | 2019-10-03 | AI Therapeutics, Inc. | Apilimod compositions and methods for using same |
| ES2734081T3 (es) * | 2014-11-07 | 2019-12-04 | Ai Therapeutics Inc | Apilimod para el uso en el tratamiento de melanoma |
| CN107249638B (zh) | 2014-11-07 | 2021-05-14 | 人工智能治疗公司 | 阿匹莫德用于治疗肾癌 |
| JP2019502707A (ja) * | 2016-01-21 | 2019-01-31 | ラム・セラピューティクス，インコーポレーテッド | 癌をアピリモドで処置するためのバイオマーカー |
| MX2019002185A (es) * | 2016-08-25 | 2019-09-19 | Ai Therapeutics Inc | Composiciones y metodos relacionados con la inhibicion de la señalizacion de rangos. |
| US20190365771A1 (en) * | 2016-10-12 | 2019-12-05 | AI Therapeutics, Inc. | Apilimod compositions and methods for using same in the treatment of alzheimer's disease |
| EP3600328A4 (en) | 2017-03-24 | 2021-01-06 | 3100 Central Expressway LLC | MERGED TRIAZOLO-PYRIMIDINE COMPOUNDS WITH USEFUL PHARMACEUTICAL APPLICATION |
| US11524053B2 (en) | 2018-01-26 | 2022-12-13 | The Regents Of The University Of California | Methods and compositions for treatment of angiogenic disorders using anti-VEGF agents |
| US12589097B2 (en) | 2018-02-21 | 2026-03-31 | OrphAl Therapeutics Inc. | Apilimod compositions and methods of use |
| US10751345B2 (en) | 2018-02-21 | 2020-08-25 | AI Therapeutics, Inc. | Combination therapy with apilimod and glutamatergic agents |
| CN114867487A (zh) | 2019-11-25 | 2022-08-05 | 加利福尼亚大学董事会 | 用于眼内新生血管的长效vegf抑制剂 |
| US12486274B2 (en) | 2020-01-13 | 2025-12-02 | Verge Analytics, Inc. | Substituted pyrazolo-pyrimidines and uses thereof |
| CN114306370A (zh) * | 2021-12-31 | 2022-04-12 | 北京悦康科创医药科技股份有限公司 | 反义寡核苷酸在制备治疗肾癌药物中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006128129A2 (en) * | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
| RU2486183C9 (ru) * | 2007-08-01 | 2014-01-27 | Байер Интеллектуэль Проперти Гмбх | Дипептидные пролекарства и их применение |
| RU2013110124A (ru) * | 2010-08-17 | 2014-09-27 | Ф.Хоффманн-Ля Рош Аг | Комбинированная противораковая терапия |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| EP0728218B1 (en) | 1993-11-12 | 2008-01-02 | PHRI Properties, Inc. | Hybridization probes for nucleic acid detection, universal stems, methods and kits |
| US6693097B2 (en) | 2001-11-30 | 2004-02-17 | Synta Pharmaceuticals Corp. | Pyrimidine compounds |
| WO2005076843A2 (en) | 2004-02-06 | 2005-08-25 | Elan Pharmaceuticals, Inc. | Methods and compositions for treating tumors and metastatic disease |
| TWI380816B (zh) | 2004-04-13 | 2013-01-01 | Synta Pharmaceuticals Corp | 抑制介白素-１２（ｉｌ-１２）生成之二鹽抑制劑 |
| JP2008512490A (ja) | 2004-09-08 | 2008-04-24 | チェルシー・セラピューティクス，インコーポレイテッド | 異常細胞増殖および炎症の障害を治療するための代謝的に不活性な葉酸拮抗剤 |
| TW200630363A (en) | 2004-11-10 | 2006-09-01 | Synta Pharmaceuticals Corp | Process for preparing trisubstituted pyrimidine compounds |
| TW200720256A (en) | 2005-05-13 | 2007-06-01 | Synta Pharmaceuticals Corp | IL-12 modulatory compounds |
| CA2630271C (en) | 2005-11-17 | 2014-04-08 | Osi Pharmaceuticals, Inc. | Fused bicyclic mtor inhibitors |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| EP1981890A2 (en) | 2006-01-25 | 2008-10-22 | OSI Pharmaceuticals, Inc. | UNSATURATED mTOR INHIBITORS |
| ES2780193T3 (es) | 2006-07-12 | 2020-08-24 | Univ Tennessee Res Found | Compuesto para tratar el cáncer de mama y afecciones dependientes de la progestina |
| CA2675558A1 (en) | 2007-02-06 | 2008-08-14 | Novartis Ag | Pi 3-kinase inhibitors and methods of their use |
| RU2438664C2 (ru) | 2007-05-15 | 2012-01-10 | Пирамал Лайф Сайнсиз Лимитед | Синергическая фармацевтическая комбинация для лечения рака |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| JP5258331B2 (ja) | 2008-03-03 | 2013-08-07 | ロート製薬株式会社 | 光安定性が改善されたニューキノロン系抗菌剤含有医薬組成物 |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| EP3023426A1 (en) | 2008-07-17 | 2016-05-25 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| EP3338770B1 (en) | 2010-03-08 | 2023-06-07 | Sloan-Kettering Institute For Cancer Research | Cdc7 kinase inhibitors and uses thereof |
| JP5783499B2 (ja) * | 2010-03-29 | 2015-09-24 | 味の素株式会社 | フェニルアラニン誘導体を含有する医薬製剤 |
| US8402515B2 (en) | 2010-05-06 | 2013-03-19 | Jonathan Weizman | Apparatus and method for establishing a peer-to-peer communication session with a client device |
| US20110287018A1 (en) | 2010-05-19 | 2011-11-24 | Philip Bosch | Methods of Treating Interstitial Cystitis |
| GEP201606545B (en) | 2010-11-19 | 2016-09-26 | Ecole Polytech | 2-piperazin-1-yl-4h-1,3-benzo-thiazin-4-one derivatives and their use for treatment of mammalian infections |
| WO2013152342A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Anti-cancer mtor inhibitor and anti-androgen combination |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US9856320B2 (en) | 2012-05-15 | 2018-01-02 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting PD-1/PD-L1 signaling |
| HK1214128A1 (zh) | 2012-10-05 | 2016-07-22 | Bluelink Pharmaceuticals, Inc. | 癌症的治療 |
| US9295731B2 (en) | 2013-04-01 | 2016-03-29 | Mark Quang Nguyen | Cleavable drug conjugates, compositions thereof and methods of use |
| AU2015209133B2 (en) | 2014-01-24 | 2019-10-03 | AI Therapeutics, Inc. | Apilimod compositions and methods for using same |
| CN107249638B (zh) | 2014-11-07 | 2021-05-14 | 人工智能治疗公司 | 阿匹莫德用于治疗肾癌 |
| ES2734081T3 (es) | 2014-11-07 | 2019-12-04 | Ai Therapeutics Inc | Apilimod para el uso en el tratamiento de melanoma |
| KR101761573B1 (ko) | 2014-12-29 | 2017-07-26 | 주식회사 인트론바이오테크놀로지 | 신규한 장출혈성 대장균 박테리오파지 Ｅｓｃ-ＣＨＰ-1 및 이의 장출혈성 대장균 증식 억제 용도 |
| WO2016126707A1 (en) | 2015-02-03 | 2016-08-11 | Lam Therapeutics, Inc. | Apilimod compositions and methods for using same |
| US20180078561A1 (en) | 2015-03-31 | 2018-03-22 | Lam Therapeutics, Inc. | Active metabolites of apilimod and uses thereof |
| TWI746449B (zh) | 2015-07-20 | 2021-11-21 | 美商Ａｉ治療公司 | 使用阿吡莫德治療癌症之方法 |
| AU2019299234A1 (en) | 2018-07-05 | 2021-01-14 | Mayo Foundation For Medical Education And Research | PIKfyve inhibitors |
| US20210077500A1 (en) | 2019-09-12 | 2021-03-18 | Al Therapeutics, Inc. | Pikfyve inhibitors for cancer therapy |
-
2015
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006128129A2 (en) * | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
| RU2486183C9 (ru) * | 2007-08-01 | 2014-01-27 | Байер Интеллектуэль Проперти Гмбх | Дипептидные пролекарства и их применение |
| RU2013110124A (ru) * | 2010-08-17 | 2014-09-27 | Ф.Хоффманн-Ля Рош Аг | Комбинированная противораковая терапия |
Non-Patent Citations (4)
| Title |
|---|
| Cai X et al. PIKfyve, a class III PI kinase, isthe target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-likereceptor signaling // Chem Biol.- 2013 Jul 25; 20(7):912-21. * |
| Cai X, et al. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling // Chem Biol.- 2013.- Jul 25; 20(7):912-21. * |
| George K. Philips, et al. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies // International Immunology. - 16.10.2014. - Volume 27, Issue 1.- Pages 39-46. Cai X et al. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling // Chem Biol.- 2013 Jul 25; 20(7):912-21. * |
| George K. Philips, et al. Therapeutic usesof anti-PD-1 and anti-PD-L1 antibodies // International Immunology. - 16.10.2014. - Volume 27, Issue 1.- Pages 39-46. * |
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| BR112017008799A2 (pt) | 2017-12-19 |
| CN107249638A (zh) | 2017-10-13 |
| PL3215158T3 (pl) | 2019-11-29 |
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| EP3581184A1 (en) | 2019-12-18 |
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| MX2017006015A (es) | 2017-11-17 |
| US11166944B2 (en) | 2021-11-09 |
| EP3581184B1 (en) | 2021-02-24 |
| KR20170098812A (ko) | 2017-08-30 |
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| IL251905A0 (en) | 2017-06-29 |
| US20190201385A1 (en) | 2019-07-04 |
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| EP3215158B1 (en) | 2019-05-08 |
| RU2017119065A (ru) | 2018-12-07 |
| JP2017535601A (ja) | 2017-11-30 |
| US20200297706A1 (en) | 2020-09-24 |
| AU2015342869A1 (en) | 2017-06-15 |
| WO2016073877A1 (en) | 2016-05-12 |
| US20170333408A1 (en) | 2017-11-23 |
| JP6705828B2 (ja) | 2020-06-03 |
| MX377593B (es) | 2025-03-10 |
| US10206910B2 (en) | 2019-02-19 |
| CN107249638B (zh) | 2021-05-14 |
| IL251905B (en) | 2021-03-25 |
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