CN104736202A - 用于抑制肌成束蛋白的方法 - Google Patents
用于抑制肌成束蛋白的方法 Download PDFInfo
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- CN104736202A CN104736202A CN201380055065.XA CN201380055065A CN104736202A CN 104736202 A CN104736202 A CN 104736202A CN 201380055065 A CN201380055065 A CN 201380055065A CN 104736202 A CN104736202 A CN 104736202A
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Abstract
Description
4T1乳腺肿瘤细胞 |
MDA-MB-231乳腺肿瘤细胞 |
DU145前列腺肿瘤细胞 |
PC-3前列腺肿瘤细胞 |
LLC肺肿瘤细胞 |
Claims (67)
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CN202110950531.7A CN113679717A (zh) | 2012-08-22 | 2013-08-21 | 用于抑制肌成束蛋白的方法 |
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US201261692177P | 2012-08-22 | 2012-08-22 | |
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US201361778015P | 2013-03-12 | 2013-03-12 | |
US61/778,015 | 2013-03-12 | ||
PCT/US2013/055965 WO2014031732A2 (en) | 2012-08-22 | 2013-08-21 | Methods for inhibiting fascin |
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EP (1) | EP2888010B1 (zh) |
JP (1) | JP6371284B2 (zh) |
CN (2) | CN104736202B (zh) |
CA (2) | CA3139033A1 (zh) |
DK (1) | DK2888010T3 (zh) |
ES (1) | ES2877570T3 (zh) |
WO (1) | WO2014031732A2 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106668008A (zh) * | 2015-11-10 | 2017-05-17 | 河南省锐达医药科技有限公司 | 基于stat3蛋白靶点的靶向抗癌药物的发明 |
CN108498503A (zh) * | 2017-02-24 | 2018-09-07 | 河南省锐达医药科技有限公司 | 一类新型细胞信号传导和基因转录激活因子3型(stat3)抑制剂的制备和用途 |
CN112912141A (zh) * | 2018-08-27 | 2021-06-04 | 斯皮诺吉尼克斯公司 | 用于树突棘生成的肌成束蛋白结合化合物 |
CN114014824A (zh) * | 2020-12-09 | 2022-02-08 | 上海科技大学 | 一种杂环化合物的应用 |
WO2023045910A1 (zh) * | 2021-09-22 | 2023-03-30 | 杭州天玑济世生物科技有限公司 | 一类具有萘硫酚醚结构的小分子化合物及其应用 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015127125A1 (en) * | 2014-02-20 | 2015-08-27 | Cornell University | Compounds and methods for inhibiting fascin |
CN108697690B (zh) * | 2016-01-05 | 2022-01-14 | 加利福尼亚大学董事会 | 苯并噻唑两亲物 |
EP3402780A1 (en) | 2016-01-14 | 2018-11-21 | Beth Israel Deaconess Medical Center, Inc. | Mast-cell modulators and uses thereof |
AU2018312558B2 (en) | 2017-08-02 | 2022-09-29 | Spinogenix, Inc. | Benzothiazole and related compounds |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070043057A1 (en) * | 2005-02-09 | 2007-02-22 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
WO2010005534A2 (en) * | 2008-06-30 | 2010-01-14 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Proteasome inhibitors for selectively inducing apoptosis in cancer cells |
US20100041685A1 (en) * | 2008-06-04 | 2010-02-18 | Tweardy David J | Stat3 inhibitors |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1244696A (en) | 1968-06-20 | 1971-09-02 | Fuji Photo Film Co Ltd | Improvements in colour developer compositions |
US4559157A (en) | 1983-04-21 | 1985-12-17 | Creative Products Resource Associates, Ltd. | Cosmetic applicator useful for skin moisturizing |
LU84979A1 (fr) | 1983-08-30 | 1985-04-24 | Oreal | Composition cosmetique ou pharmaceutique sous forme aqueuse ou anhydre dont la phase grasse contient un polyether oligomere et polyethers oligomeres nouveaux |
US4820508A (en) | 1987-06-23 | 1989-04-11 | Neutrogena Corporation | Skin protective composition |
US4786644A (en) * | 1987-11-27 | 1988-11-22 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryl-3-quinolinecarboxamide |
US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
WO1995026325A2 (en) | 1994-03-25 | 1995-10-05 | Isotechnika Inc. | Enhancement of the efficacy of drugs by deuteration |
US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
AU1324300A (en) * | 1998-10-26 | 2000-05-15 | Vertex Pharmaceuticals Incorporated | Pentacyclic compounds useful as inhibitors of hepatitis c virus ns3 helicase |
GB9902455D0 (en) | 1999-02-05 | 1999-03-24 | Zeneca Ltd | Chemical compounds |
US20040009613A1 (en) * | 2001-02-16 | 2004-01-15 | Ming-Ming Zhou | Methods of identifying modulators of bromodomains |
TWI262920B (en) | 2000-10-27 | 2006-10-01 | Elbion Ag | New 7-azaindoles, their use as inhibitors of phosphodiesterase 4, and a method for synthesizing them |
JP2005510492A (ja) | 2001-10-26 | 2005-04-21 | ユニバーシティ オブ コネチカット | 新規な種類の効力のあるカンナビミメティックリガンド |
ES2275918T3 (es) * | 2001-11-08 | 2007-06-16 | Ortho-Mcneil Pharmaceutical, Inc. | Derivados del 1,2,4-tiazol novedosos como moduladores de los receptores de la melanocortina. |
US20050209252A1 (en) * | 2002-03-29 | 2005-09-22 | Che-Ming Teng | Cancer treatment |
US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
RU2006109108A (ru) | 2003-10-14 | 2007-11-20 | Оксаген Лимитед (GB) | Соединения, обладающие активностью антагонистов crth2 рецепторов |
US20050130974A1 (en) * | 2003-10-17 | 2005-06-16 | Rigel Pharmaceuticals, Inc. | Benzothiazole compositions and their use as ubiquitin ligase inhibitors |
JP2007523197A (ja) * | 2004-02-23 | 2007-08-16 | プロレキシーズ ファーマシューティカルズ インコーポレイテッド | pHSP20様活性を有する非ペプチジル剤、およびその使用 |
TW200612918A (en) | 2004-07-29 | 2006-05-01 | Threshold Pharmaceuticals Inc | Lonidamine analogs |
DE602005027228D1 (de) * | 2004-10-21 | 2011-05-12 | Burnham Inst La Jolla | Zusammensetzungen und verfahren zur behandlung von krankheiten, die durch infektion mit yersinia spp ausgelöst sind |
EP2079466B1 (en) | 2006-09-29 | 2014-01-15 | GlaxoSmithKline LLC | Substituted indole compounds |
US7858645B2 (en) | 2006-11-01 | 2010-12-28 | Hoffmann-La Roche Inc. | Indazole derivatives |
EP2089355A2 (en) | 2006-11-01 | 2009-08-19 | Brystol-Myers Squibb Company | Modulators of glucocorticoid receptor, ap-1, and/or nf- kappa b activity and use thereof |
CN101594862B (zh) | 2006-12-20 | 2015-11-25 | 内尔维阿诺医学科学有限公司 | 作为激酶抑制剂的取代吲唑衍生物 |
WO2008089310A2 (en) | 2007-01-18 | 2008-07-24 | Lexicon Pharmaceuticals, Inc. | Delta 5 desaturase inhibitors for the treatment of obesity |
WO2008129276A1 (en) * | 2007-04-19 | 2008-10-30 | Boehringer Ingelheim International Gmbh | Disulfonamides useful in the treatment of inflammation |
CN101918036A (zh) | 2007-11-21 | 2010-12-15 | 康奈尔大学 | 抑制肌成束蛋白的方法 |
WO2009085549A2 (en) | 2007-12-21 | 2009-07-09 | Sandisk Corporation | Self-configurable multi-regulator asic core power delivery |
EP2219646A4 (en) * | 2007-12-21 | 2010-12-22 | Univ Rochester | METHOD FOR MODIFYING THE LIFETIME OF EUKARYOTIC ORGANISMS |
CU20080028A6 (es) * | 2008-02-29 | 2011-02-24 | Ct Ingenieria Genetica Biotech | Compuestos químicos obtenidos in silico para la preparación de composiciones farmacéuticas para atenuar o inhibir la infección por virus dengue y otros flavivirus |
AU2009231258A1 (en) | 2008-04-04 | 2009-10-08 | Biomarin Iga Limited | Compounds for treating muscular dystrophy |
US20110218158A1 (en) * | 2008-09-22 | 2011-09-08 | Harris Reuben S | Dna cytosine deaminase inhibitors |
JO3101B1 (ar) | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
WO2010102286A2 (en) * | 2009-03-06 | 2010-09-10 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Proteasome inhibitors having chymotrypsin-like activity |
US8785499B2 (en) | 2009-07-10 | 2014-07-22 | University Of Maryland, Baltimore | Targeting NAD biosynthesis in bacterial pathogens |
ES2360783B1 (es) * | 2009-10-02 | 2012-07-04 | Consejo Superior De Investigaciones Científicas (Csic) | 1,2,4-tiadiazoles-5-imino sustituidos utiles en el tratamiento de enfermedades neurodegenerativas |
KR101632318B1 (ko) | 2009-11-05 | 2016-06-27 | 재단법인 의약바이오컨버젼스연구단 | 벤조헤테로사이클 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 암 예방 및 치료용 조성물 |
JP5937968B2 (ja) * | 2010-01-29 | 2016-06-22 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | Mcl‐1を調節する小分子、並びに細胞死、細胞分裂、細胞分化を調節する方法、及び疾患を治療する方法。 |
WO2011133862A1 (en) * | 2010-04-23 | 2011-10-27 | Oregon Health And Science University | Methods and compositions for promoting myelination |
DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
ES2553610T3 (es) * | 2010-12-14 | 2015-12-10 | Electrophoretics Limited | Inhibidores de la caseína cinasa 1 delta (CK1delta) |
ES2618812T3 (es) | 2011-01-20 | 2017-06-22 | Merck Sharp & Dohme Corp. | Antagonistas del receptor mineralocorticoide |
JP6256772B2 (ja) | 2012-12-19 | 2018-01-10 | セルジーン クオンティセル リサーチ,インク. | ヒストンデメチラーゼ阻害剤 |
-
2013
- 2013-08-21 CA CA3139033A patent/CA3139033A1/en active Pending
- 2013-08-21 US US13/972,649 patent/US10208043B2/en active Active
- 2013-08-21 WO PCT/US2013/055965 patent/WO2014031732A2/en active Application Filing
- 2013-08-21 EP EP13830441.5A patent/EP2888010B1/en active Active
- 2013-08-21 ES ES13830441T patent/ES2877570T3/es active Active
- 2013-08-21 CN CN201380055065.XA patent/CN104736202B/zh active Active
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- 2013-08-21 CN CN202110950531.7A patent/CN113679717A/zh active Pending
- 2013-08-21 JP JP2015528615A patent/JP6371284B2/ja active Active
- 2013-08-21 CA CA2881554A patent/CA2881554C/en active Active
-
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- 2019-02-15 US US16/277,691 patent/US10941146B2/en active Active
-
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- 2021-01-28 US US17/160,948 patent/US11866440B2/en active Active
-
2023
- 2023-12-21 US US18/393,556 patent/US20240158402A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070043057A1 (en) * | 2005-02-09 | 2007-02-22 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
US20100041685A1 (en) * | 2008-06-04 | 2010-02-18 | Tweardy David J | Stat3 inhibitors |
WO2010005534A2 (en) * | 2008-06-30 | 2010-01-14 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Proteasome inhibitors for selectively inducing apoptosis in cancer cells |
Non-Patent Citations (3)
Title |
---|
JIE QIN等: "Identification of a Novel Family of BRAFV600E Inhibitors", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
MOSTAFA M. GHORAB等: "Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer and radioprotective activity", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
STN: "REGISTRY NUMBERS:6628-24-3、70375-43-8等", 《STN:FILE REGISTRY》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106668008A (zh) * | 2015-11-10 | 2017-05-17 | 河南省锐达医药科技有限公司 | 基于stat3蛋白靶点的靶向抗癌药物的发明 |
CN108498503A (zh) * | 2017-02-24 | 2018-09-07 | 河南省锐达医药科技有限公司 | 一类新型细胞信号传导和基因转录激活因子3型(stat3)抑制剂的制备和用途 |
CN112912141A (zh) * | 2018-08-27 | 2021-06-04 | 斯皮诺吉尼克斯公司 | 用于树突棘生成的肌成束蛋白结合化合物 |
CN114014824A (zh) * | 2020-12-09 | 2022-02-08 | 上海科技大学 | 一种杂环化合物的应用 |
WO2023045910A1 (zh) * | 2021-09-22 | 2023-03-30 | 杭州天玑济世生物科技有限公司 | 一类具有萘硫酚醚结构的小分子化合物及其应用 |
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US20210332051A1 (en) | 2021-10-28 |
EP2888010B1 (en) | 2021-05-19 |
US20200017506A1 (en) | 2020-01-16 |
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WO2014031732A2 (en) | 2014-02-27 |
ES2877570T3 (es) | 2021-11-17 |
JP2015526472A (ja) | 2015-09-10 |
US11866440B2 (en) | 2024-01-09 |
EP2888010A4 (en) | 2016-07-20 |
US20140080843A1 (en) | 2014-03-20 |
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US10941146B2 (en) | 2021-03-09 |
CA2881554A1 (en) | 2014-02-27 |
WO2014031732A3 (en) | 2014-05-01 |
CN104736202B (zh) | 2021-09-07 |
CA2881554C (en) | 2022-01-04 |
EP2888010A2 (en) | 2015-07-01 |
US10208043B2 (en) | 2019-02-19 |
JP6371284B2 (ja) | 2018-08-08 |
CN113679717A (zh) | 2021-11-23 |
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