JP5053503B2 - 過増殖状態を処置するための方法および組成物 - Google Patents
過増殖状態を処置するための方法および組成物 Download PDFInfo
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- JP5053503B2 JP5053503B2 JP2003567445A JP2003567445A JP5053503B2 JP 5053503 B2 JP5053503 B2 JP 5053503B2 JP 2003567445 A JP2003567445 A JP 2003567445A JP 2003567445 A JP2003567445 A JP 2003567445A JP 5053503 B2 JP5053503 B2 JP 5053503B2
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- Prior art keywords
- phenyl
- pyrrolo
- benzyloxy
- pyrimidin
- amino
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| AR035885A1 (es) | 2001-05-14 | 2004-07-21 | Novartis Ag | Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica |
| ATE514434T1 (de) * | 2004-02-25 | 2011-07-15 | Dana Farber Cancer Inst Inc | Hemmer des insulinartigen wachstumsfaktor- rezeptors-1 zur hemmung von tumorzellwachstum |
| TWI378934B (en) | 2004-04-02 | 2012-12-11 | Osi Pharm Inc | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| US7329495B2 (en) | 2004-06-09 | 2008-02-12 | Board Of Regents, The University Of Texas System | Mutations in KIT confer imatinib resistance in gastrointestinal stromal tumors |
| TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| CA2783656A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2783665A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| EP2544672A1 (en) | 2010-03-09 | 2013-01-16 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス，インク． | 癌治療 |
| US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ226799A (en) * | 1987-11-06 | 1991-08-27 | Oncogen | Breast cancer inhibitory factor and method for inhibiting proliferation of neoplastic cells and compositions therefor |
| DE4129533A1 (de) * | 1991-09-05 | 1993-03-11 | Max Planck Gesellschaft | Mutierter wachstumsfaktorrezeptor als arzneimittel und seine verwendung zur behandlung von krebs |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| CN1117097C (zh) * | 1998-05-29 | 2003-08-06 | 北京金赛狮生物制药技术开发有限责任公司 | 类胰岛素生长因子受体基因的反义核酸的抑癌作用 |
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2003
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- 2003-02-14 CA CA002476000A patent/CA2476000A1/en not_active Abandoned
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- 2003-02-14 AU AU2003205768A patent/AU2003205768A1/en not_active Abandoned
- 2003-02-14 AT AT03702642T patent/ATE360442T1/de active
- 2003-02-14 DE DE60313434T patent/DE60313434T2/de not_active Expired - Lifetime
- 2003-02-14 CN CN03803734A patent/CN100591355C/zh not_active Expired - Fee Related
- 2003-02-14 PT PT03702642T patent/PT1476192E/pt unknown
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- 2003-02-14 WO PCT/EP2003/001507 patent/WO2003068265A1/en not_active Ceased
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| Publication number | Publication date |
|---|---|
| DE60313434T2 (de) | 2008-01-10 |
| CN100591355C (zh) | 2010-02-24 |
| CA2476000A1 (en) | 2003-08-21 |
| PT1476192E (pt) | 2007-07-26 |
| DE60313434D1 (de) | 2007-06-06 |
| JP2005517040A (ja) | 2005-06-09 |
| ES2283744T3 (es) | 2007-11-01 |
| WO2003068265A1 (en) | 2003-08-21 |
| CN1630534A (zh) | 2005-06-22 |
| ATE360442T1 (de) | 2007-05-15 |
| EP1476192B1 (en) | 2007-04-25 |
| BR0307629A (pt) | 2005-01-11 |
| AU2003205768A1 (en) | 2003-09-04 |
| EP1476192A1 (en) | 2004-11-17 |
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