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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| PT3215157T (pt) * | 2014-11-07 | 2019-07-12 | Ai Therapeutics Inc | Apilimod para utilização no tratamento de melanoma |
| US10206910B2 (en) | 2014-11-07 | 2019-02-19 | Lam Therapeutics, Inc. | Apilimod for use in the treatment of renal cancer |
| BR112018009738A2 (pt) * | 2016-01-21 | 2018-12-04 | Lam Therapeutics Inc | biomarcadores para tratamento contra o câncer com apilimod |
| CA3034453A1 (en) * | 2016-08-25 | 2018-03-01 | AI Therapeutics, Inc. | Compositions comprising pikfyve inhibitors and methods related to inhibition of rank signaling |
| RU2019113752A (ru) * | 2016-10-12 | 2020-11-13 | ЭйАй ТЕРАПЬЮТИКС, ИНК. | Композиции апилимода и способы их применения при лечении болезни альцгеймера |
| KR102642378B1 (ko) | 2017-03-24 | 2024-02-28 | 픽사이 인코포레이티드 | 유용한 약학적 적용을 갖는 융합된 트리아졸로-피리미딘 화합물 |
| 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 |
| AU2019223014B2 (en) | 2018-02-21 | 2024-10-17 | Orphai Therapeutics Inc. | Combination therapy with apilimod and glutamatergic agents |
| AU2020393842A1 (en) | 2019-11-25 | 2022-06-16 | The Regents Of The University Of California | Long-acting VEGF inhibitors for intraocular neovascularization |
| CA3167339A1 (en) | 2020-01-13 | 2021-07-22 | 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 |
| EP2423322A1 (en) | 1993-11-12 | 2012-02-29 | 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 |
| US7745436B2 (en) | 2004-04-13 | 2010-06-29 | Synta Pharmaceuticals Corporation | Disalt inhibitors of IL-12 production |
| WO2006029385A2 (en) | 2004-09-08 | 2006-03-16 | Chelsea Therapeutics, Inc. | Quinazoline derivatives as metabolically inert antifolate compounds. |
| WO2006053112A1 (en) | 2004-11-10 | 2006-05-18 | Synta Pharmaceuticals Corp. | Process for preparing trisubstituted pyrimidine compounds |
| US7863270B2 (en) | 2005-05-13 | 2011-01-04 | Synta Pharmaceuticals Corp. | IL-12 modulatory compounds |
| ES2436877T3 (es) | 2005-11-17 | 2014-01-07 | OSI Pharmaceuticals, LLC | Intermedios para la preparación de inhibidores de mTOR bicíclicos condensados |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| US7659274B2 (en) | 2006-01-25 | 2010-02-09 | Osi Pharmaceuticals, Inc. | Unsaturated mTOR inhibitors |
| HUE032274T2 (en) | 2006-07-12 | 2017-09-28 | Univ Tennessee Res Found | Substituted acetanilides and methods of their application |
| AU2008213808B2 (en) | 2007-02-06 | 2011-11-10 | 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 |
| WO2010006072A2 (en) | 2008-07-08 | 2010-01-14 | The Regents Of The University Of California | Mtor modulators and uses thereof |
| CA2730890C (en) | 2008-07-17 | 2018-05-15 | Critical Outcome Technologies Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| CN102844023B (zh) | 2010-03-08 | 2016-01-20 | 索隆-基特林癌症研究协会 | Cdc7激酶抑制剂以及其用途 |
| ES2768349T3 (es) * | 2010-03-29 | 2020-06-22 | Ea Pharma Co Ltd | Preparación farmacéutica que comprende un derivado de fenilalanina |
| 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 |
| WO2011146727A1 (en) | 2010-05-19 | 2011-11-24 | Philip Bosch | Methods of treating interstitial cystitis |
| US8796264B2 (en) | 2010-11-19 | 2014-08-05 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4H-1,3-benzothiazin-4-one derivatives and their use for the 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 |
| AU2013263076B2 (en) | 2012-05-15 | 2017-08-31 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting PD-1/PD-L1 signaling |
| EP2903644A4 (en) | 2012-10-05 | 2016-03-09 | Cerulean Pharma Inc | TREATMENT OF CANCER |
| US9295731B2 (en) | 2013-04-01 | 2016-03-29 | Mark Quang Nguyen | Cleavable drug conjugates, compositions thereof and methods of use |
| RU2016134406A (ru) | 2014-01-24 | 2018-03-01 | Лэм Терапьютикс, Инк. | Композиции апилимода и способы их применения |
| US10206910B2 (en) | 2014-11-07 | 2019-02-19 | Lam Therapeutics, Inc. | Apilimod for use in the treatment of renal cancer |
| PT3215157T (pt) | 2014-11-07 | 2019-07-12 | Ai Therapeutics Inc | Apilimod para utilização no tratamento 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 |
| EP3253389A4 (en) | 2015-02-03 | 2018-07-18 | 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 |
| WO2020009971A1 (en) | 2018-07-05 | 2020-01-09 | Mayo Foundation For Medical Education And Research | Pikfyve inhibitors |
| AR119934A1 (es) | 2019-09-12 | 2022-01-19 | Ai Therapeutics Inc | Inhibidores de pikfyve para terapia contra el cáncer |
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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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| US11166944B2 (en) | 2021-11-09 |
| CN107249638A (zh) | 2017-10-13 |
| PL3215158T3 (pl) | 2019-11-29 |
| ES2741399T3 (es) | 2020-02-10 |
| HUE044557T2 (hu) | 2019-11-28 |
| CN107249638B (zh) | 2021-05-14 |
| EP3215158B1 (en) | 2019-05-08 |
| EP3581184A1 (en) | 2019-12-18 |
| CA2966359A1 (en) | 2016-05-12 |
| WO2016073877A1 (en) | 2016-05-12 |
| BR112017008799A2 (pt) | 2017-12-19 |
| US10206910B2 (en) | 2019-02-19 |
| US20170333408A1 (en) | 2017-11-23 |
| RU2017119065A (ru) | 2018-12-07 |
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