成纤维细胞生长因子受体
成纤维细胞生长因子受体1
化学
苯并咪唑
成纤维细胞生长因子
IC50型
受体
体外
成纤维细胞
生长因子受体
药理学
癌症研究
生长抑制
生物化学
生物
有机化学
作者
Wei Yan,Xinyi Wang,Yang Dai,Bin Zhao,Yang Xia,Jianling Fan,Yijun Gao,Fanwang Meng,Yuming Wang,Cheng Luo,Jing Ai,Meiyu Geng,Wenhu Duan
标识
DOI:10.1021/acs.jmedchem.6b00056
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.
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