JP2013522326A - がん幹細胞を標的とするための新規の方法 - Google Patents
がん幹細胞を標的とするための新規の方法 Download PDFInfo
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- A61P35/00—Antineoplastic agents
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| JP2014098049A (ja) * | 2010-03-19 | 2014-05-29 | Boston Biomedical Inc | がん幹細胞を標的とするための新規の化合物および組成物 |
| WO2015190489A1 (ja) * | 2014-06-09 | 2015-12-17 | 京都薬品工業株式会社 | 新規抗癌剤 |
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| HRP20160625T1 (hr) | 2007-09-10 | 2016-08-12 | Boston Biomedical, Inc. | Novi inhibitori stat3 signalnog puta i inhibitori matičnih stanica raka |
| CA2908380A1 (en) | 2013-04-09 | 2014-10-16 | Boston Biomedical, Inc. | Methods for treating cancer |
| WO2015120304A1 (en) | 2014-02-07 | 2015-08-13 | Boston Biomedical, Inc. | 3-substituted carbonyl-naphtho[2,3-b]furane derivative or pharmaceutically acceptable salt thereof |
| JP2018511645A (ja) | 2015-04-17 | 2018-04-26 | ボストン バイオメディカル， インコーポレイテッド | 癌を治療するための方法 |
| JP2018511643A (ja) | 2015-04-17 | 2018-04-26 | ボストン バイオメディカル， インコーポレイテッド | 癌を治療するための方法 |
| TW201717935A (zh) | 2015-06-03 | 2017-06-01 | 波士頓生醫公司 | 用於治療癌症的組成物和方法 |
| JP6871919B2 (ja) | 2015-06-16 | 2021-05-19 | ナノファギックス エルエルシー | 薬物送達及びイメージング化学コンジュゲート、製剤及びその使用方法 |
| WO2017013270A1 (en) | 2015-07-23 | 2017-01-26 | Universite De Strasbourg | Use of leptin signaling inhibitor for protecting kidneys from patients having ciliopathy |
| EP3405189A1 (en) | 2016-01-20 | 2018-11-28 | Boston Biomedical, Inc. | Methods for treating cancer |
| WO2018005444A2 (en) | 2016-06-28 | 2018-01-04 | Boston Biomedical, Inc. | Methods for treating cancer |
| WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
| WO2018102427A1 (en) | 2016-11-29 | 2018-06-07 | Boston Biomedical, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
| WO2018213424A1 (en) | 2017-05-17 | 2018-11-22 | Boston Biomedical, Inc. | Methods for treating cancer |
| EP3762391A4 (en) * | 2018-03-08 | 2022-08-03 | ExxonMobil Technology and Engineering Company | SPIROCENTRIC COMPOUNDS AND POLYMERS THEREOF |
| JP7513286B2 (ja) | 2018-10-12 | 2024-07-09 | １グローブ バイオメディカル カンパニー， リミテッド | 化学療法難治性がんの治療のための新しい併用薬方法 |
| 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 |
| CN117350965A (zh) * | 2023-10-07 | 2024-01-05 | 中国原子能科学研究院 | 对象内放射性微球的指标预估装置 |
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| WO2009036099A1 (en) * | 2007-09-10 | 2009-03-19 | Boston Biomedical, Inc. | A novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors |
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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 |
| EP1146869A2 (en) | 1999-01-27 | 2001-10-24 | University Of South Florida | Inhibition of stat3 signal transduction for human cancer therapy |
| US6482943B1 (en) | 1999-04-30 | 2002-11-19 | Slil Biomedical Corporation | Quinones as disease therapies |
| MXPA02000828A (es) | 1999-08-02 | 2002-07-30 | Hoffmann La Roche | Nuevos antagonistas retinoiides selectivos. |
| 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 |
| WO2002078617A2 (en) | 2001-03-28 | 2002-10-10 | 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 |
| WO2003045357A1 (en) | 2001-11-27 | 2003-06-05 | Transform Pharmaceuticals, Inc. | Oral pharmaceutical formulations comprising paclitaxel, derivatives and methods of administration thereof |
| EP1990055A3 (en) * | 2001-11-29 | 2011-11-16 | Therakos, Inc. | Methods for pretreating a subject with extracorporeal photopheresis and/or apoptotic cells |
| AU2003215524A1 (en) | 2002-03-15 | 2003-09-29 | Natimmune A/S | Pharmaceutical compositions comprising mannose binding lectin |
| US20060142271A1 (en) * | 2002-09-17 | 2006-06-29 | Klaus Muller | Novel lapacho compounds and methods of use thereof |
| TWI335913B (en) * | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
| IS6633A (is) | 2002-11-22 | 2004-05-23 | Omega Farma Ehf. | Samsetningar af fínasteríð töflum |
| US20060019256A1 (en) | 2003-06-09 | 2006-01-26 | 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 |
| MXPA06006460A (es) | 2003-12-11 | 2006-08-23 | Univ Texas | Compuestos para el tratamiento de enfermedades proliferativas celulares. |
| 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 |
| AU2005309019A1 (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 |
| CA2599393A1 (en) | 2005-02-25 | 2006-08-31 | The Regents 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 |
| RU2456265C2 (ru) | 2006-03-31 | 2012-07-20 | Дзе Борд Оф Риджентс Оф Дзе Юниверсити Оф Техас Систем | Биологически доступная для перорального применения кофейная кислота, относящаяся к противоопухолевым лекарственным средствам |
| 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 |
| RU2657750C1 (ru) * | 2010-03-19 | 2018-06-15 | Бостон Байомедикал, Инк. | Новые способы направленного воздействия на раковые стволовые клетки |
-
2011
- 2011-03-21 ES ES11757135T patent/ES2987670T3/es active Active
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-
2017
- 2017-07-05 US US15/642,105 patent/US20170319537A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009036099A1 (en) * | 2007-09-10 | 2009-03-19 | Boston Biomedical, Inc. | A novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors |
| JP2010539098A (ja) * | 2007-09-10 | 2010-12-16 | ボストン バイオメディカル， インコーポレイテッド | 癌治療のための新規の組成物および方法 |
| JP2010539095A (ja) * | 2007-09-10 | 2010-12-16 | ボストン バイオメディカル， インコーポレイテッド | 新規のＳｔａｔ３経路阻害剤及び癌幹細胞阻害剤 |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014098049A (ja) * | 2010-03-19 | 2014-05-29 | Boston Biomedical Inc | がん幹細胞を標的とするための新規の化合物および組成物 |
| WO2015190489A1 (ja) * | 2014-06-09 | 2015-12-17 | 京都薬品工業株式会社 | 新規抗癌剤 |
| JPWO2015190489A1 (ja) * | 2014-06-09 | 2017-05-25 | 京都薬品工業株式会社 | 新規抗癌剤 |
| US10005752B2 (en) | 2014-06-09 | 2018-06-26 | Kyoto Pharmaceutical Industries, Ltd. | Anticancer agent |
| US10377730B2 (en) | 2014-06-09 | 2019-08-13 | Kyoto Pharmaceutical Industries, Ltd. | Anticancer agent |
| JP2019206529A (ja) * | 2014-06-09 | 2019-12-05 | 京都薬品工業株式会社 | 新規抗癌剤 |
| US10689355B2 (en) | 2014-06-09 | 2020-06-23 | Kyoto Pharmaceuticals Industries, Ltd. | Anticancer agent |
| US11267797B2 (en) | 2014-06-09 | 2022-03-08 | Kyoto Pharmaceutical Industries, Ltd. | Anticancer agent |
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| SMT202400193T1 (it) | 2024-07-09 |
| EP2547205B1 (en) | 2024-03-20 |
| HRP20240658T1 (hr) | 2024-08-16 |
| BR112012023660B1 (pt) | 2021-05-18 |
| WO2011116399A1 (en) | 2011-09-22 |
| US20130028944A1 (en) | 2013-01-31 |
| US20170319537A1 (en) | 2017-11-09 |
| AU2011227023A1 (en) | 2012-09-27 |
| US9730909B2 (en) | 2017-08-15 |
| BR112012023660A2 (pt) | 2015-09-15 |
| LT2547205T (lt) | 2024-06-10 |
| RU2591823C2 (ru) | 2016-07-20 |
| CA2946890A1 (en) | 2011-09-22 |
| PL2547205T3 (pl) | 2024-07-08 |
| DK2547205T3 (da) | 2024-05-27 |
| FI2547205T3 (fi) | 2024-05-27 |
| RS65536B1 (sr) | 2024-06-28 |
| EP2547205A1 (en) | 2013-01-23 |
| ES2987670T3 (es) | 2024-11-15 |
| SI2547205T1 (sl) | 2024-08-30 |
| EP2547205A4 (en) | 2013-08-14 |
| RU2012144420A (ru) | 2014-04-27 |
| AU2011227023B2 (en) | 2015-05-28 |
| BR112012023660B8 (pt) | 2021-05-25 |
| CN103025159A (zh) | 2013-04-03 |
| CA2793527A1 (en) | 2011-09-22 |
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