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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| 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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| CN105963289B (zh) | 2007-09-10 | 2021-02-26 | 北京强新生物科技有限公司 | 一类stat3通路抑制剂和癌干细胞通路抑制剂 |
| CN106211758B (zh) * | 2013-04-09 | 2021-03-23 | 北京强新生物科技有限公司 | 2-乙酰基萘并[2,3-b]呋喃-4,9-二酮用于治疗癌症的用途 |
| CN106163284A (zh) | 2014-02-07 | 2016-11-23 | 北京强新生物科技有限公司 | 3‑取代的羰基萘并[2,3‑b]呋喃衍生物或其药学上可接受的盐 |
| EA201792288A1 (ru) | 2015-04-17 | 2018-02-28 | Бостон Биомедикал, Инк. | Способы лечения рака |
| WO2016168856A1 (en) | 2015-04-17 | 2016-10-20 | Boston Biomedical, Inc. | Methods for treating cancer |
| 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 |
| EP3310786B1 (en) | 2015-06-16 | 2021-03-03 | Nanophagix LLC | Drug delivery and imaging chemical conjugate, formulations and methods of use thereof |
| WO2017013270A1 (en) | 2015-07-23 | 2017-01-26 | Universite De Strasbourg | Use of leptin signaling inhibitor for protecting kidneys from patients having ciliopathy |
| US20190076392A1 (en) | 2016-01-20 | 2019-03-14 | Boston Biomedical, Inc. | Methods for treating cancer |
| JP2019519573A (ja) | 2016-06-28 | 2019-07-11 | ボストン バイオメディカル， インコーポレイテッド | がんを処置するための方法 |
| WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
| US11299469B2 (en) | 2016-11-29 | 2022-04-12 | Sumitomo Dainippon Pharma Oncology, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
| JP2020520923A (ja) | 2017-05-17 | 2020-07-16 | ボストン バイオメディカル， インコーポレイテッド | がんを処置するための方法 |
| US10953369B2 (en) * | 2018-03-08 | 2021-03-23 | Georgia Tech Research Corporation | Spirocentric compounds and polymers thereof |
| AU2019357933B2 (en) | 2018-10-12 | 2023-11-23 | 1Globe Biomedical Co., Ltd. | New combination solution for treating chemotherapy refractory cancer |
| 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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| 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 |
| DK1206436T3 (da) | 1999-08-02 | 2005-02-14 | Hoffmann La Roche | Retinoider til behandling af emfysem |
| 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 |
| WO2003045357A1 (en) | 2001-11-27 | 2003-06-05 | Transform Pharmaceuticals, Inc. | Oral pharmaceutical formulations comprising paclitaxel, derivatives and methods of administration thereof |
| US20030139466A1 (en) | 2001-11-29 | 2003-07-24 | Peritt David L. | Methods for pretreating a subject with extracorporeal photopheresis |
| US7462596B2 (en) | 2002-03-15 | 2008-12-09 | Natimmune A/S | Pharmaceutical compositions comprising mannose binding lectin |
| WO2004026253A2 (en) | 2002-09-17 | 2004-04-01 | Arqule, Inc. | Novel lapacho compounds and methods of use thereof |
| AR042052A1 (es) | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| 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 |
| CN102603565A (zh) | 2003-12-11 | 2012-07-25 | 得克萨斯州大学系统董事会 | 治疗细胞增殖疾病的化合物 |
| CA2563305A1 (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 |
| KR20070085433A (ko) | 2004-11-24 | 2007-08-27 | 노파르티스 아게 | Ｊａｋ 저해제들과 ｂｃｒ-ａｂｌ, ｆｌｔ-3, ｆａｋ 또는ｒａｆ 키나제 저해제들 중 하나 이상의 조합물 |
| 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 |
| US20070243192A1 (en) | 2006-02-21 | 2007-10-18 | 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 |
| WO2008094321A2 (en) | 2006-10-04 | 2008-08-07 | Universtiy 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 |
| WO2009060282A2 (en) | 2007-11-06 | 2009-05-14 | Orchid Research Laboratories Limited | Stilbene derivatives as pstat3/il-6 inhibitors |
| HUE066482T2 (hu) * | 2010-03-19 | 2024-08-28 | 1Globe Biomedical Co Ltd | Új eljárások rákõssejtek megcélzására |
-
2011
- 2011-03-21 ES ES11757135T patent/ES2987670T3/es active Active
- 2011-03-21 EP EP11757135.6A patent/EP2547205B1/en active Active
- 2011-03-21 WO PCT/US2011/029283 patent/WO2011116399A1/en not_active Ceased
- 2011-03-21 JP JP2013500247A patent/JP2013522326A/ja active Pending
- 2011-03-21 LT LTEPPCT/US2011/029283T patent/LT2547205T/lt unknown
- 2011-03-21 BR BR112012023660A patent/BR112012023660B8/pt active IP Right Grant
- 2011-03-21 RU RU2012144420/15A patent/RU2591823C2/ru active
- 2011-03-21 DK DK11757135.6T patent/DK2547205T3/da active
- 2011-03-21 SM SM20240193T patent/SMT202400193T1/it unknown
- 2011-03-21 AU AU2011227023A patent/AU2011227023B2/en active Active
- 2011-03-21 PL PL11757135.6T patent/PL2547205T3/pl unknown
- 2011-03-21 US US13/634,694 patent/US9730909B2/en not_active Expired - Fee Related
- 2011-03-21 CA CA2946890A patent/CA2946890A1/en not_active Abandoned
- 2011-03-21 RS RS20240574A patent/RS65536B1/sr unknown
- 2011-03-21 SI SI201132110T patent/SI2547205T1/sl unknown
- 2011-03-21 HR HRP20240658TT patent/HRP20240658T1/hr unknown
- 2011-03-21 CA CA2793527A patent/CA2793527A1/en not_active Abandoned
- 2011-03-21 CN CN2011800233152A patent/CN103025159A/zh active Pending
- 2011-03-21 FI FIEP11757135.6T patent/FI2547205T3/fi active
-
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 |
Also Published As
| Publication number | Publication date |
|---|---|
| SMT202400193T1 (it) | 2024-07-09 |
| EP2547205B1 (en) | 2024-03-20 |
| HRP20240658T1 (hr) | 2024-08-16 |
| EP2547205A4 (en) | 2013-08-14 |
| RU2591823C2 (ru) | 2016-07-20 |
| US9730909B2 (en) | 2017-08-15 |
| AU2011227023A1 (en) | 2012-09-27 |
| BR112012023660B1 (pt) | 2021-05-18 |
| AU2011227023B2 (en) | 2015-05-28 |
| LT2547205T (lt) | 2024-06-10 |
| CA2946890A1 (en) | 2011-09-22 |
| ES2987670T3 (es) | 2024-11-15 |
| RU2012144420A (ru) | 2014-04-27 |
| EP2547205A1 (en) | 2013-01-23 |
| DK2547205T3 (da) | 2024-05-27 |
| BR112012023660A2 (pt) | 2015-09-15 |
| BR112012023660B8 (pt) | 2021-05-25 |
| CN103025159A (zh) | 2013-04-03 |
| RS65536B1 (sr) | 2024-06-28 |
| FI2547205T3 (fi) | 2024-05-27 |
| US20130028944A1 (en) | 2013-01-31 |
| CA2793527A1 (en) | 2011-09-22 |
| US20170319537A1 (en) | 2017-11-09 |
| WO2011116399A1 (en) | 2011-09-22 |
| PL2547205T3 (pl) | 2024-07-08 |
| SI2547205T1 (sl) | 2024-08-30 |
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