CA2856803A1 - Enhanced treatment regimens using mtor inhibitors - Google Patents
Enhanced treatment regimens using mtor inhibitors Download PDFInfo
- Publication number
- CA2856803A1 CA2856803A1 CA2856803A CA2856803A CA2856803A1 CA 2856803 A1 CA2856803 A1 CA 2856803A1 CA 2856803 A CA2856803 A CA 2856803A CA 2856803 A CA2856803 A CA 2856803A CA 2856803 A1 CA2856803 A1 CA 2856803A1
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- CA
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- Prior art keywords
- aryl
- 10alkyl
- nr31r32
- heterocyclyl
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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Applications Claiming Priority (3)
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| US201161563516P | 2011-11-23 | 2011-11-23 | |
| US61/563,516 | 2011-11-23 | ||
| PCT/US2012/066431 WO2013078440A2 (en) | 2011-11-23 | 2012-11-21 | Enhanced treatment regimens using mtor inhibitors |
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| CA2856803A1 true CA2856803A1 (en) | 2013-05-30 |
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| CA2856803A Abandoned CA2856803A1 (en) | 2011-11-23 | 2012-11-21 | Enhanced treatment regimens using mtor inhibitors |
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| WO (1) | WO2013078440A2 (OSRAM) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130209543A1 (en) * | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| WO2015050957A2 (en) * | 2013-10-02 | 2015-04-09 | Treatments For Systemic Lupus Erythematosus | Treatments for systemic lupus erythematosus |
| JP2016536282A (ja) * | 2013-10-03 | 2016-11-24 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ＰＩ３Ｋα阻害剤を使用する強化された治療レジメン |
| WO2015148615A1 (en) * | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of bronchiolitis obliterans syndrome |
| WO2015148623A1 (en) * | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of fibrotic respiratory disorders |
| WO2015148626A1 (en) * | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of fibrotic disorders |
| WO2016183398A1 (en) * | 2015-05-13 | 2016-11-17 | Memorial Sloan Kettering Cancer Center | Macropinocytosis in cancer |
| JP7034084B2 (ja) | 2016-03-28 | 2022-03-11 | インサイト・コーポレイション | Ｔａｍ阻害剤としてのピロロトリアジン化合物 |
| RS62322B1 (sr) | 2016-04-15 | 2021-10-29 | Cancer Research Tech Ltd | Heterociklična jedinjenja kao inhibitori ret kinaze |
| LT3442535T (lt) | 2016-04-15 | 2022-10-25 | Cancer Research Technology Limited | Heterocikliniai junginiai kaip ret kinazės inhibitoriai |
| GB201705971D0 (en) * | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| UY37900A (es) | 2017-09-26 | 2019-04-30 | Novartis Ag | Nuevos derivados de rapamicina |
| FR3075795A1 (fr) | 2017-12-21 | 2019-06-28 | Galderma Research & Development | Nouveaux composes inhibiteurs de mtor |
| EP3849535A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| FI3898637T3 (fi) | 2018-12-18 | 2025-02-24 | Novartis Ag | Rapamysiinijohdannaisia |
| ES2987625T3 (es) | 2019-03-26 | 2024-11-15 | Novartis Ag | Derivados de rapamicina que contienen 1,1-dióxido de isotiazolidina y 1,4-butanosultona y usos de los mismos |
| US20210205322A1 (en) * | 2020-01-08 | 2021-07-08 | Albert Einstein College Of Medicine | Rictor-targeted therapy in the management of brain metastases |
| JP2023529867A (ja) | 2020-06-05 | 2023-07-12 | キネート バイオファーマ インク． | 線維芽細胞増殖因子受容体キナーゼの阻害剤 |
| CN116515988A (zh) * | 2023-03-21 | 2023-08-01 | 中南大学湘雅二医院 | 用于评估长期使用糖皮质激素后t淋巴细胞功能的标志物 |
| WO2024249380A2 (en) * | 2023-05-26 | 2024-12-05 | University Of Vermont And State Agricultural College | 1h-pyrazolo[3,4-d]pyrimidin-4-amines as anti-infectious agents |
Family Cites Families (122)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1219606A (en) | 1968-07-15 | 1971-01-20 | Rech S Et D Applic Scient Soge | Quinuclidinol derivatives and preparation thereof |
| US3657744A (en) | 1970-05-08 | 1972-04-25 | Univ Minnesota | Method for fixing prosthetic implants in a living body |
| US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
| US5061273A (en) | 1989-06-01 | 1991-10-29 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US5350395A (en) | 1986-04-15 | 1994-09-27 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US4748982A (en) | 1987-01-06 | 1988-06-07 | Advanced Cardiovascular Systems, Inc. | Reinforced balloon dilatation catheter with slitted exchange sleeve and method |
| CA1322628C (en) | 1988-10-04 | 1993-10-05 | Richard A. Schatz | Expandable intraluminal graft |
| GB8916480D0 (en) | 1989-07-19 | 1989-09-06 | Glaxo Group Ltd | Chemical process |
| US5292331A (en) | 1989-08-24 | 1994-03-08 | Applied Vascular Engineering, Inc. | Endovascular support device |
| US5674278A (en) | 1989-08-24 | 1997-10-07 | Arterial Vascular Engineering, Inc. | Endovascular support device |
| US6344053B1 (en) | 1993-12-22 | 2002-02-05 | Medtronic Ave, Inc. | Endovascular support device and method |
| GB8923590D0 (en) | 1989-10-19 | 1989-12-06 | Pfizer Ltd | Antimuscarinic bronchodilators |
| CS277070B6 (en) | 1989-12-22 | 1992-11-18 | Adamovske Strojirny Np | Device for the control of printing pressures |
| PT100441A (pt) | 1991-05-02 | 1993-09-30 | Smithkline Beecham Corp | Pirrolidinonas, seu processo de preparacao, composicoes farmaceuticas que as contem e uso |
| WO1993019751A1 (en) | 1992-04-02 | 1993-10-14 | Smithkline Beecham Corporation | Compounds useful for treating inflammatory diseases and inhibiting production of tumor necrosis factor |
| CA2133439C (en) | 1992-04-02 | 2005-07-26 | Siegfried Benjamin Christensen, Iv | Compounds useful for treating allergic and inflammatory diseases |
| WO1993019750A1 (en) | 1992-04-02 | 1993-10-14 | Smithkline Beecham Corporation | Compounds useful for treating allergic or inflammatory diseases |
| GB9301000D0 (en) | 1993-01-20 | 1993-03-10 | Glaxo Group Ltd | Chemical compounds |
| GB9414208D0 (en) | 1994-07-14 | 1994-08-31 | Glaxo Group Ltd | Compounds |
| GB9414193D0 (en) | 1994-07-14 | 1994-08-31 | Glaxo Group Ltd | Compounds |
| US5759787A (en) | 1996-08-26 | 1998-06-02 | Tularik Inc. | Kinase assay |
| GB9622386D0 (en) | 1996-10-28 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| TW528755B (en) | 1996-12-24 | 2003-04-21 | Glaxo Group Ltd | 2-(purin-9-yl)-tetrahydrofuran-3,4-diol derivatives |
| US6166037A (en) | 1997-08-28 | 2000-12-26 | Merck & Co., Inc. | Pyrrolidine and piperidine modulators of chemokine receptor activity |
| AU9281298A (en) | 1997-10-01 | 1999-04-23 | Kyowa Hakko Kogyo Co. Ltd. | Benzodioxole derivatives |
| GB9723566D0 (en) | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| GB9723589D0 (en) | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| GB9723590D0 (en) | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| YU44900A (sh) | 1998-01-31 | 2003-01-31 | Glaxo Group Limited | Derivati 2-(purin-9-il)tetrahidrofuran-3,4-diola |
| AR017457A1 (es) | 1998-02-14 | 2001-09-05 | Glaxo Group Ltd | Compuestos derivados de 2-(purin-9-il)-tetrahidrofuran-3,4-diol, procesos para su preparacion, composiciones que los contienen y su uso en terapia para el tratamiento de enfermedades inflamatorias. |
| GB9813540D0 (en) | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
| GB9813535D0 (en) | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
| SK19542000A3 (sk) | 1998-06-23 | 2001-09-11 | Glaxo Group Limited | 2-(purin-9-yl)-tetrahydrofurn-3,4-diolov derivty, spsob ich vroby, farmaceutick prostriedok s ich obsahom, ich pouitie a medziprodukty |
| GB9813565D0 (en) | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
| EP1098923B1 (en) | 1998-06-30 | 2004-11-17 | Dow Global Technologies Inc. | Polymer polyols and a process for the production thereof |
| BR9914526A (pt) | 1998-10-16 | 2001-07-03 | Pfizer | Derivados de adenina |
| GB9913083D0 (en) | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
| DE60021370C5 (de) | 1999-05-04 | 2007-11-08 | Schering Corp. | Piperazinderivate verwendbar als ccr5 antagonisten |
| HK1039330B (en) | 1999-05-04 | 2005-12-09 | Schering Corporation | Piperidine derivatives useful as ccr5 antagonists |
| YU25500A (sh) | 1999-05-11 | 2003-08-29 | Pfizer Products Inc. | Postupak za sintezu analoga nukleozida |
| GB9913932D0 (en) | 1999-06-15 | 1999-08-18 | Pfizer Ltd | Purine derivatives |
| US6322771B1 (en) | 1999-06-18 | 2001-11-27 | University Of Virginia Patent Foundation | Induction of pharmacological stress with adenosine receptor agonists |
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| HRP20020158B1 (en) | 1999-08-21 | 2007-08-31 | Altana Pharma Ag | Action of synergistic combination |
| CO5180581A1 (es) | 1999-09-30 | 2002-07-30 | Pfizer Prod Inc | Compuestos para el tratamiento de la isquemia ciones farmaceuticas que los contienen para el tratamiento de la isquemia |
| CA2386374A1 (en) | 1999-10-07 | 2001-04-12 | Carlos Estuardo Aguilar-Cordova | Methods for treatment of solid tumors and metastasis by gene therapy |
| GB9924363D0 (en) | 1999-10-14 | 1999-12-15 | Pfizer Central Res | Purine derivatives |
| GB9924361D0 (en) | 1999-10-14 | 1999-12-15 | Pfizer Ltd | Purine derivatives |
| GB0003960D0 (en) | 2000-02-18 | 2000-04-12 | Pfizer Ltd | Purine derivatives |
| TWI227240B (en) | 2000-06-06 | 2005-02-01 | Pfizer | 2-aminocarbonyl-9H-purine derivatives |
| GB0015727D0 (en) | 2000-06-27 | 2000-08-16 | Pfizer Ltd | Purine derivatives |
| SI1300407T2 (sl) | 2000-06-27 | 2011-09-30 | S A L V A T Lab Sa | Karbamati, izvedeni iz arilalkilaminov |
| GB0015876D0 (en) | 2000-06-28 | 2000-08-23 | Novartis Ag | Organic compounds |
| DE10038639A1 (de) | 2000-07-28 | 2002-02-21 | Schering Ag | Nichtsteroidale Entzündungshemmer |
| CA2417826A1 (en) | 2000-08-05 | 2002-02-14 | Glaxo Group Limited | 17.beta.-carbothioate 17.alpha.-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents |
| GB0022695D0 (en) | 2000-09-15 | 2000-11-01 | Pfizer Ltd | Purine Derivatives |
| US20030165902A1 (en) * | 2000-09-29 | 2003-09-04 | Bieglecki Karyn M. | Haplotypes of the F2R gene |
| US6423546B1 (en) * | 2000-11-02 | 2002-07-23 | Miller Brewing Company | Monoclonal antibodies for assaying lipid transfer proteins |
| WO2002063046A1 (en) * | 2000-11-09 | 2002-08-15 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the tacr2 gene |
| AU2002245073A1 (en) * | 2000-11-10 | 2002-07-24 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the f2rli gene |
| GB0028383D0 (en) | 2000-11-21 | 2001-01-03 | Novartis Ag | Organic compounds |
| JP4445704B2 (ja) | 2000-12-22 | 2010-04-07 | アルミラル・ソシエダッド・アノニマ | キヌクリジンカルバメート誘導体およびｍ３アンダゴニストとしてのそれらの使用 |
| KR100869721B1 (ko) | 2000-12-28 | 2008-11-21 | 알미랄 에이쥐 | 신규한 퀴누클리딘 유도체 및 그를 함유한 의약 조성물 |
| EP1241176A1 (en) | 2001-03-16 | 2002-09-18 | Pfizer Products Inc. | Purine derivatives for the treatment of ischemia |
| PL366937A1 (en) | 2001-04-30 | 2005-02-07 | Glaxo Group Limited | Anti-inflammatory 17.beta.-carbothioate ester derivatives of androstane with a cyclic ester group in position 17.alpha |
| SV2003001055A (es) | 2001-05-25 | 2003-11-14 | Pfizer | Un agonista de a2a en combinacion con un agente anticolinergico para el tratamiento de enfermedades obstructivas de las vias areas |
| EP1395604B1 (en) | 2001-06-12 | 2008-06-25 | Glaxo Group Limited | Novel anti inflammatory 17.alpha.-heterocyclic-esters of 17.beta.-carbothioate androstane derivatives |
| EP2327766B1 (en) | 2001-06-21 | 2015-12-02 | BASF Enzymes LLC | Nitrilases |
| EP1438309A1 (en) | 2001-10-17 | 2004-07-21 | Ucb, S.A. | Quinuclidine derivatives, processes for preparing them and their uses as m2 and/or m3 muscarinic receptor inhibitors |
| GB0125259D0 (en) | 2001-10-20 | 2001-12-12 | Glaxo Group Ltd | Novel compounds |
| AR037517A1 (es) | 2001-11-05 | 2004-11-17 | Novartis Ag | Derivados de naftiridinas, un proceso para su preparacion, composicion farmaceutica y el uso de los mismos para la preparacion de un medicamento para el tratamiento de una enfermedad inflamatoria |
| AU2002356759A1 (en) | 2001-12-01 | 2003-06-17 | Glaxo Group Limited | 17.alpha. -cyclic esters of 16-methylpregnan-3,20-dione as anti-inflammatory agents |
| US7452904B2 (en) | 2001-12-20 | 2008-11-18 | Chiesi Farmaceutici S.P.A. | 1-alkyl-1-azoniabicyclo' 2.2.2 octane carbamate derivatives and their use as muscarinic receptor antagonists |
| AU2003202044A1 (en) | 2002-01-15 | 2003-09-09 | Glaxo Group Limited | 17.alpha-cycloalkyl/cycloylkenyl esters of alkyl-or haloalkyl-androst-4-en-3-on-11.beta.,17.alpha.-diol 17.beta.-carboxylates as anti-inflammatory agents |
| WO2003062259A2 (en) | 2002-01-21 | 2003-07-31 | Glaxo Group Limited | Non-aromatic 17.alpha.-esters of androstane-17.beta.-carboxylate esters as anti-inflammatory agents |
| GB0202216D0 (en) | 2002-01-31 | 2002-03-20 | Glaxo Group Ltd | Novel compounds |
| AU2003230700A1 (en) | 2002-03-26 | 2003-10-13 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| ES2298508T3 (es) | 2002-03-26 | 2008-05-16 | Boehringer Ingelheim Pharmaceuticals Inc. | Mimeticos de glucocorticoides, metodos para prepararlos, composiciones farmaceuticas y sus usos. |
| WO2003086408A1 (en) | 2002-04-10 | 2003-10-23 | University Of Virginia Patent Foundation | Use of a2a adenosine receptor agonists for the treatment of inflammatory diseases |
| ES2206021B1 (es) | 2002-04-16 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de pirrolidinio. |
| ES2201907B1 (es) | 2002-05-29 | 2005-06-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de indolilpiperidina como potentes agentes antihistaminicos y antialergicos. |
| DE10224888A1 (de) | 2002-06-05 | 2003-12-24 | Merck Patent Gmbh | Pyridazinderivate |
| US7074806B2 (en) | 2002-06-06 | 2006-07-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| DE10225574A1 (de) | 2002-06-10 | 2003-12-18 | Merck Patent Gmbh | Aryloxime |
| DE10227269A1 (de) | 2002-06-19 | 2004-01-08 | Merck Patent Gmbh | Thiazolderivate |
| US7153968B2 (en) | 2002-06-25 | 2006-12-26 | Merck Frosst Canada, Ltd. | 8-(biaryl)quinoline PDE4 inhibitors |
| AU2003281219A1 (en) | 2002-07-02 | 2004-01-23 | Bernard Cote | Di-aryl-substituted-ethane pyridone pde4 inhibitors |
| ES2204295B1 (es) | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
| JP4503436B2 (ja) | 2002-07-08 | 2010-07-14 | ファイザー・プロダクツ・インク | 糖質コルチコイド受容体のモジュレーター |
| PE20050130A1 (es) | 2002-08-09 | 2005-03-29 | Novartis Ag | Compuestos organicos |
| PL373597A1 (en) | 2002-08-10 | 2005-09-05 | Altana Pharma Ag | Piperidine-n-oxide-derivatives |
| KR101131684B1 (ko) | 2002-08-10 | 2012-03-28 | 니코메드 게엠베하 | Ｐｄｅ４ 억제제로서의 피롤리딘디온 치환된피페리딘-프탈라존 |
| JP2005538138A (ja) | 2002-08-10 | 2005-12-15 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４インヒビターとしてのピリダジノン誘導体 |
| SE0202483D0 (sv) | 2002-08-21 | 2002-08-21 | Astrazeneca Ab | Chemical compounds |
| US7288562B2 (en) | 2002-08-23 | 2007-10-30 | Ranbaxy Laboratories Limited | Fluoro and sulphonylamino containing 3,6-disubstituted azabicyclo (3.1.0) hexane derivatives as muscarinic receptor antagonists |
| WO2004019945A1 (en) | 2002-08-29 | 2004-03-11 | Altana Pharma Ag | 3-hydroxy-6-phenylphenanthridines as pde-4 inhibitors |
| EP1539164B1 (en) | 2002-08-29 | 2006-12-20 | ALTANA Pharma AG | 2-hydroxy-6-phenylphenanthridines as pde-4 inhibitors |
| US20050267114A1 (en) | 2002-09-18 | 2005-12-01 | Yoshikazu Takaoka | Triazaspiro[5.5]undecane derivatives and drugs comprising the same as the active ingredient |
| JP2006096662A (ja) | 2002-09-18 | 2006-04-13 | Sumitomo Pharmaceut Co Ltd | 新規６−置換ウラシル誘導体及びアレルギー性疾患の治療剤 |
| JP2004107299A (ja) | 2002-09-20 | 2004-04-08 | Japan Energy Corp | 新規１−置換ウラシル誘導体及びアレルギー性疾患の治療剤 |
| DE10246374A1 (de) | 2002-10-04 | 2004-04-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Betamimetika mit verlängerter Wirkungsdauer, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| MXPA05004432A (es) | 2002-10-23 | 2005-11-23 | Glenmark Pharmaceuticals Ltd | Compuestos triciclicos novedosos utiles para el tratamiento de desordenes inflamatorios y alergicos, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen. |
| GB0225535D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Medicinal compounds |
| GB0225540D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Medicinal compounds |
| DE10253282A1 (de) | 2002-11-15 | 2004-05-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittel zur Behandlung von chronisch obstruktiver Lungenerkrankung |
| DE10253426B4 (de) | 2002-11-15 | 2005-09-22 | Elbion Ag | Neue Hydroxyindole, deren Verwendung als Inhibitoren der Phosphodiesterase 4 und Verfahren zu deren Herstellung |
| DE10253220A1 (de) | 2002-11-15 | 2004-05-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Dihydroxy-Methyl-Phenyl-Derivate, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| US7727752B2 (en) | 2003-07-29 | 2010-06-01 | Life Technologies Corporation | Kinase and phosphatase assays |
| SG135193A1 (en) * | 2003-08-18 | 2007-09-28 | Pfizer Prod Inc | Dosing schedule for erbb2 anticancer agents |
| CA2574530A1 (en) | 2004-07-23 | 2006-01-26 | Ge Healthcare Uk Limited | Cell cycle phase markers comprising phosphorylated subcellular localization domain (psld) of human dna helicase b (hdhb) |
| AU2006316605B2 (en) | 2005-11-17 | 2012-04-26 | Osi Pharmaceuticals, Inc. | Fused bicyclic mTOR inhibitors |
| US7659274B2 (en) * | 2006-01-25 | 2010-02-09 | Osi Pharmaceuticals, Inc. | Unsaturated mTOR inhibitors |
| US7651687B2 (en) | 2006-03-13 | 2010-01-26 | Osi Pharmaceuticals, Inc. | Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors |
| US8138191B2 (en) * | 2007-01-11 | 2012-03-20 | Critical Outcome Technologies Inc. | Inhibitor compounds and cancer treatment methods |
| JP2010532756A (ja) | 2007-07-06 | 2010-10-14 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | ｍＴＯＲＣ１及びｍＴＯＲＣ２の両方の阻害剤を含む組み合わせ抗癌療法 |
| WO2009058895A1 (en) | 2007-10-30 | 2009-05-07 | Syndax Pharmaceuticals, Inc. | Administration of an inhibitor of hdac and an mtor inhibitor |
| ES2627677T3 (es) * | 2008-10-31 | 2017-07-31 | Novartis Ag | Combinación de un inhibidor de fosfatidilinositol-3-cinasa (PI3K) y un inhibidor de mTOR |
| US8476282B2 (en) * | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| JP2013509444A (ja) * | 2009-10-30 | 2013-03-14 | アリアド・ファーマシューティカルズ・インコーポレイテッド | がんの治療方法及び治療用組成物 |
| EP2776441A4 (en) * | 2011-11-08 | 2015-04-08 | Intellikine Llc | TREATMENT METHOD WITH MULTIPLE PHARMACEUTICAL AGENTS |
| US9700619B2 (en) * | 2011-11-11 | 2017-07-11 | Duke University | Combination drug therapy for the treatment of solid tumors |
| US20130209543A1 (en) * | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
-
2012
- 2012-11-21 US US13/683,967 patent/US20130209543A1/en not_active Abandoned
- 2012-11-21 CN CN201280067718.1A patent/CN104363914A/zh active Pending
- 2012-11-21 US US14/360,267 patent/US9174994B2/en active Active
- 2012-11-21 CA CA2856803A patent/CA2856803A1/en not_active Abandoned
- 2012-11-21 HK HK15103955.0A patent/HK1203378A1/xx unknown
- 2012-11-21 JP JP2014543592A patent/JP6130391B2/ja active Active
- 2012-11-21 WO PCT/US2012/066431 patent/WO2013078440A2/en not_active Ceased
- 2012-11-21 EP EP12851154.0A patent/EP2793893A4/en not_active Withdrawn
-
2015
- 2015-10-15 US US14/884,120 patent/US9669032B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20160038497A1 (en) | 2016-02-11 |
| WO2013078440A2 (en) | 2013-05-30 |
| JP2015500209A (ja) | 2015-01-05 |
| EP2793893A2 (en) | 2014-10-29 |
| US20130209543A1 (en) | 2013-08-15 |
| US9174994B2 (en) | 2015-11-03 |
| HK1203378A1 (en) | 2015-10-30 |
| WO2013078440A3 (en) | 2014-09-25 |
| CN104363914A (zh) | 2015-02-18 |
| JP6130391B2 (ja) | 2017-05-17 |
| US20140287031A1 (en) | 2014-09-25 |
| US9669032B2 (en) | 2017-06-06 |
| EP2793893A4 (en) | 2015-07-08 |
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