CA2793527A1 - Use of naphthofuran derivatives in the treatment of cancer - Google Patents
Use of naphthofuran derivatives in the treatment of cancer Download PDFInfo
- Publication number
- CA2793527A1 CA2793527A1 CA2793527A CA2793527A CA2793527A1 CA 2793527 A1 CA2793527 A1 CA 2793527A1 CA 2793527 A CA2793527 A CA 2793527A CA 2793527 A CA2793527 A CA 2793527A CA 2793527 A1 CA2793527 A1 CA 2793527A1
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- cancer
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| EP3102036A4 (en) | 2014-02-07 | 2017-09-20 | Boston Biomedical, Inc. | 3-substituted carbonyl-naphtho[2,3-b]furane derivative or pharmaceutically acceptable salt thereof |
| CA2951627A1 (en) * | 2014-06-09 | 2015-12-17 | Kyoto Pharmaceutical Industries, Ltd. | Naphthofuran derivatives as anticancer agent |
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| CN111825644B (zh) * | 2019-04-18 | 2023-07-28 | 中国医学科学院药物研究所 | 2,3-二氢萘并[2,3-b]呋喃-4,9-二酮类化合物及其制备方法和用途 |
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| WO2005005601A2 (en) | 2003-06-09 | 2005-01-20 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| US20050049207A1 (en) | 2003-09-03 | 2005-03-03 | Kaufmann Doug A. | Method of treating and preventing cancer |
| WO2005033048A2 (en) | 2003-09-29 | 2005-04-14 | The Johns Hopkins University | Wnt pathway antagonists |
| CA2548152C (en) | 2003-12-11 | 2013-09-10 | Board Of Regents, The University Of Texas System | Compounds for treatment of cell proliferative diseases |
| EP1748772A2 (en) | 2004-04-09 | 2007-02-07 | University Of South Florida | Combination therapies for cancer and proliferative angiopathies |
| JP2004224802A (ja) | 2004-04-21 | 2004-08-12 | Japan Science & Technology Agency | 抗菌剤 |
| WO2006056399A2 (en) | 2004-11-24 | 2006-06-01 | Novartis Ag | Combinations of jak inhibitors and at least one of bcr-abl, flt-3, fak or raf kinase inhibitors |
| WO2006091837A2 (en) | 2005-02-25 | 2006-08-31 | The Regent Of The University Of Michigan | Small molecule inhibitors of stat3 and the uses thereof |
| JP2006248978A (ja) | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
| CN101142202A (zh) * | 2005-03-16 | 2008-03-12 | 太日保日本株式会社 | 抗癌化合物及其中间体和生产方法 |
| JP2006290871A (ja) | 2005-03-16 | 2006-10-26 | Taheebo Japan Kk | 抗癌性を示す化合物およびその中間体ならびにそれらの製造方法 |
| US20060252073A1 (en) | 2005-04-18 | 2006-11-09 | Regents Of The University Of Michigan | Compositions and methods for the treatment of cancer |
| WO2007100640A2 (en) | 2006-02-21 | 2007-09-07 | The Regents Of The University Of Michigan | Growth hormone receptor antagonist cancer treatment |
| ES2533383T3 (es) | 2006-03-31 | 2015-04-09 | The Board Of Regents Of The University Of Texas System | Fármacos anticancerosos biodisponibles por vía oral relacionados con ácido cafeico |
| US20070238770A1 (en) | 2006-04-05 | 2007-10-11 | Bristol-Myers Squibb Company | Process for preparing novel crystalline forms of peliglitazar, novel stable forms produced therein and formulations |
| US8828451B2 (en) | 2006-10-04 | 2014-09-09 | University Of South Florida | Akt sensitization of cancer cells |
| JP4077863B1 (ja) | 2007-05-31 | 2008-04-23 | タヒボジャパン株式会社 | 抗癌活性を有する光学活性２−（１−ヒドロキシエチル）−５−ヒドロキシナフト［２，３−ｂ］フラン−４，９−ジオンの製法 |
| HRP20160949T1 (hr) | 2007-09-10 | 2016-10-07 | Boston Biomedical, Inc. | Novi sastavi i metode za liječenje karcinoma |
| US20100298402A1 (en) | 2007-11-06 | 2010-11-25 | Orchid Research Laboratories Limited | Stilbene derivatives as pstat3/il-6 inhibitors |
| RU2657750C1 (ru) * | 2010-03-19 | 2018-06-15 | Бостон Байомедикал, Инк. | Новые способы направленного воздействия на раковые стволовые клетки |
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2011
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- 2011-03-21 CA CA2793527A patent/CA2793527A1/en not_active Abandoned
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- 2011-03-21 FI FIEP11757135.6T patent/FI2547205T3/fi active
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- 2011-03-21 RS RS20240574A patent/RS65536B1/sr unknown
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- 2011-03-21 SI SI201132110T patent/SI2547205T1/sl unknown
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10377731B2 (en) | 2007-09-10 | 2019-08-13 | Boston Biomedical, Inc. | Compositions and methods for cancer treatment |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112012023660B8 (pt) | 2021-05-25 |
| CN103025159A (zh) | 2013-04-03 |
| RS65536B1 (sr) | 2024-06-28 |
| LT2547205T (lt) | 2024-06-10 |
| PL2547205T3 (pl) | 2024-07-08 |
| AU2011227023B2 (en) | 2015-05-28 |
| ES2987670T3 (es) | 2024-11-15 |
| BR112012023660B1 (pt) | 2021-05-18 |
| HRP20240658T1 (hr) | 2024-08-16 |
| JP2013522326A (ja) | 2013-06-13 |
| US20170319537A1 (en) | 2017-11-09 |
| DK2547205T3 (da) | 2024-05-27 |
| CA2946890A1 (en) | 2011-09-22 |
| RU2012144420A (ru) | 2014-04-27 |
| AU2011227023A1 (en) | 2012-09-27 |
| US20130028944A1 (en) | 2013-01-31 |
| BR112012023660A2 (pt) | 2015-09-15 |
| FI2547205T3 (fi) | 2024-05-27 |
| US9730909B2 (en) | 2017-08-15 |
| SMT202400193T1 (it) | 2024-07-09 |
| EP2547205B1 (en) | 2024-03-20 |
| EP2547205A1 (en) | 2013-01-23 |
| WO2011116399A1 (en) | 2011-09-22 |
| SI2547205T1 (sl) | 2024-08-30 |
| RU2591823C2 (ru) | 2016-07-20 |
| EP2547205A4 (en) | 2013-08-14 |
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