Discovery of 3-(5 '-substituted)-benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1h-indazoles as potent fibroblast growth factor receptor inhibitors: design, synthesis, and biological evaluation
文献类型：期刊论文
| 作者 | Yan, Wei1; Wang, Xinyi2,6; Dai, Yang2; Zhao, Bin3; Yang, Xinying2; Fan, Jun3; Gao, Yinglei2; Meng, Fanwang4,5; Wang, Yuming3; Luo, Cheng |
| 刊名 | Journal of medicinal chemistry
 |
| 出版日期 | 2016-07-28 |
| 卷号 | 59期号:14页码:6690-6708 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b00056 |
| 通讯作者 | Ai, jing(jai@simm.ac.cn) ; Geng, meiyu(mygeng@simm.ac.cn) ; Duan, wenhu(whduan@simm.ac.cn) |
| 英文摘要 | Fibroblast growth factor receptor (fgfr) represents an attractive oncology target for cancer therapy in view of its critical role in promoting cancer formation and progression, as well as causing resistance to approved therapies. in this article, we describe the identification of the potent pan-fgfr inhibitor (r)-21c (fgfr1-4 ic50 values of 0.9, 2.0, 2.0, and 6.1 nm, respectively). compound (r)-21c exhibited excellent in vitro inhibitory activity against a panel of fgfr-amplified cell lines. western blot analysis demonstrated that (r)-21c suppressed fgf/fgfr and downstream signaling pathways at nanomolar concentrations. moreover, (r)-21c provided nearly complete inhibition of tumor growth (96.9% tgi) in nci-h1581 (fgfr1-amplified) xenograft mice model at the dose of 10 mg/kg/qd via oral administration. |
| WOS关键词 | TYROSINE KINASE ; SELECTIVE INHIBITOR ; HEPATOCELLULAR-CARCINOMA ; ANTIANGIOGENIC THERAPY ; CELL CARCINOMA ; BREAST-CANCER ; RESISTANCE ; FGFR ; ANGIOGENESIS ; EXPRESSION |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000380730600008 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375122 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Ai, Jing; Geng, Meiyu; Duan, Wenhu |
| 作者单位 | 1.East China Univ Sci & Technol, Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 4.Shanghai Univ, Coll Sci, Dept Chem, 99 Shang Da Rd, Shanghai 200111, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yan, Wei,Wang, Xinyi,Dai, Yang,et al. Discovery of 3-(5 '-substituted)-benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1h-indazoles as potent fibroblast growth factor receptor inhibitors: design, synthesis, and biological evaluation[J]. Journal of medicinal chemistry,2016,59(14):6690-6708. |
| APA | Yan, Wei.,Wang, Xinyi.,Dai, Yang.,Zhao, Bin.,Yang, Xinying.,...&Duan, Wenhu.(2016).Discovery of 3-(5 '-substituted)-benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1h-indazoles as potent fibroblast growth factor receptor inhibitors: design, synthesis, and biological evaluation.Journal of medicinal chemistry,59(14),6690-6708. |
| MLA | Yan, Wei,et al."Discovery of 3-(5 '-substituted)-benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1h-indazoles as potent fibroblast growth factor receptor inhibitors: design, synthesis, and biological evaluation".Journal of medicinal chemistry 59.14(2016):6690-6708. |
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来源：中国科学院大学
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