RU2591823C2 - Новые способы направленного воздействия на раковые стволовые клетки - Google Patents
Новые способы направленного воздействия на раковые стволовые клетки Download PDFInfo
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- RU2591823C2 RU2591823C2 RU2012144420/15A RU2012144420A RU2591823C2 RU 2591823 C2 RU2591823 C2 RU 2591823C2 RU 2012144420/15 A RU2012144420/15 A RU 2012144420/15A RU 2012144420 A RU2012144420 A RU 2012144420A RU 2591823 C2 RU2591823 C2 RU 2591823C2
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|---|---|---|---|---|
| EP0402192A1 (fr) | 1989-05-31 | 1990-12-12 | BODET, Jean Augustin | Article en carton ou matière analogue et procédé de fabrication |
| JPH04139177A (ja) | 1989-12-28 | 1992-05-13 | Dainippon Ink & Chem Inc | フラルベンゾキノン誘導体及びその製造方法並びに制癌剤 |
| JPH1121284A (ja) | 1997-06-30 | 1999-01-26 | Kotobuki:Kk | フラノナフトキノン誘導体及びこれを含有する医薬 |
| US6174913B1 (en) | 1998-06-05 | 2001-01-16 | The University Of North Carolina At Chapel Hill | Naphtho- and dihydrobenzo-thiophene derivatives as cytotoxic antitumor agents |
| JP2003525862A (ja) | 1999-01-27 | 2003-09-02 | ザ ユニヴァーシティー オブ サウス フロリダ | ヒト癌の治療のためのｓｔａｔ３シグナル伝達の阻害 |
| US6482943B1 (en) | 1999-04-30 | 2002-11-19 | Slil Biomedical Corporation | Quinones as disease therapies |
| PT1206436E (pt) | 1999-08-02 | 2004-12-31 | Hoffmann La Roche | Retinoides para o tratamento de enfisema |
| JP2001097860A (ja) | 1999-09-29 | 2001-04-10 | Japan Science & Technology Corp | 抗薬剤耐性菌剤と抗クラミジア剤 |
| UA75055C2 (uk) | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| AU2002307217A1 (en) | 2001-03-28 | 2002-10-15 | University Of South Florida | Materials and methods for treatment of cancer and identification of anti-cancer compounds |
| GB0117696D0 (en) * | 2001-07-20 | 2001-09-12 | Bradford Particle Design Plc | Particle information |
| AU2002357012A1 (en) | 2001-11-27 | 2003-06-10 | Transform Pharmaceuticals, Inc. | Oral pharmaceutical formulations comprising paclitaxel, derivatives and methods of administration thereof |
| CN1310652C (zh) | 2001-11-29 | 2007-04-18 | 特拉科斯有限公司 | 用体外光提取法和/或凋亡细胞对被试者进行预治疗的方法 |
| AU2003215524A1 (en) | 2002-03-15 | 2003-09-29 | Natimmune A/S | Pharmaceutical compositions comprising mannose binding lectin |
| EP1551392A4 (en) | 2002-09-17 | 2006-09-20 | Arqule Inc | NEW LAPACHO COMPOUNDS AND APPLICATION METHOD THEREFOR |
| IS6633A (is) | 2002-11-22 | 2004-05-23 | Omega Farma Ehf. | Samsetningar af fínasteríð töflum |
| EP2003196A3 (en) | 2003-06-09 | 2009-01-07 | 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 |
| DK1701941T3 (da) | 2003-12-11 | 2012-08-13 | Univ Texas | Forbindelser til behandling af sygdomme med celleproliferation |
| WO2005110477A2 (en) | 2004-04-09 | 2005-11-24 | 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 |
| BRPI0517887A (pt) | 2004-11-24 | 2008-10-21 | Novartis Ag | combinações de inibidores de jaks |
| 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 |
| 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 |
| 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 |
| 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 |
| US8779151B2 (en) | 2006-03-31 | 2014-07-15 | The Board Of Regents Of The University Of Texas System | Orally bioavailable caffeic acid related anticancer drugs |
| 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 |
| US20100298402A1 (en) | 2007-11-06 | 2010-11-25 | Orchid Research Laboratories Limited | Stilbene derivatives as pstat3/il-6 inhibitors |
| CN104016951B (zh) * | 2010-03-19 | 2016-07-13 | 北京强新生物科技有限公司 | 靶向癌症干细胞的化合物和组合物 |
-
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- 2011-03-21 CA CA2946890A patent/CA2946890A1/en not_active Abandoned
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2350606C2 (ru) * | 2002-11-15 | 2009-03-27 | Вертекс Фармасьютикалз Инкорпорейтед | Диаминотриазолы, пригодные в качестве ингибиторов протеинкиназ |
| WO2009036099A1 (en) * | 2007-09-10 | 2009-03-19 | Boston Biomedical, Inc. | A novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| PINZON-GUZMAN C. et al. "Protein kinase C regulates rod photoreceptor differentiation through modulation of STAT3 signaling." Adv Exp Med Biol. 2010;664:21-8. doi: 10.1007/978-1-4419-1399-9_3, реферат, [найдено 13.03.2015], найдено из PubMed PMID:20237998. LING X et al. "Mesenchymal Stem Cells Overexpressing IFN-β? Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model". Cancer Microenviron. 2010 Mar 19;3(1):83-95. doi: 10.1007/s12307-010-0041-8. реферат, [найдено 13.03.2015], найдено из PubMed PMID:21209776. * |
Also Published As
| Publication number | Publication date |
|---|---|
| RS65536B1 (sr) | 2024-06-28 |
| BR112012023660A2 (pt) | 2015-09-15 |
| BR112012023660B1 (pt) | 2021-05-18 |
| FI2547205T3 (fi) | 2024-05-27 |
| AU2011227023B2 (en) | 2015-05-28 |
| EP2547205A1 (en) | 2013-01-23 |
| US20130028944A1 (en) | 2013-01-31 |
| EP2547205B1 (en) | 2024-03-20 |
| CA2793527A1 (en) | 2011-09-22 |
| JP2013522326A (ja) | 2013-06-13 |
| PL2547205T3 (pl) | 2024-07-08 |
| CA2946890A1 (en) | 2011-09-22 |
| DK2547205T3 (da) | 2024-05-27 |
| SMT202400193T1 (it) | 2024-07-09 |
| WO2011116399A1 (en) | 2011-09-22 |
| BR112012023660B8 (pt) | 2021-05-25 |
| CN103025159A (zh) | 2013-04-03 |
| SI2547205T1 (sl) | 2024-08-30 |
| EP2547205A4 (en) | 2013-08-14 |
| HRP20240658T1 (hr) | 2024-08-16 |
| LT2547205T (lt) | 2024-06-10 |
| US9730909B2 (en) | 2017-08-15 |
| ES2987670T3 (es) | 2024-11-15 |
| AU2011227023A1 (en) | 2012-09-27 |
| US20170319537A1 (en) | 2017-11-09 |
| RU2012144420A (ru) | 2014-04-27 |
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