Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer

被引：12

作者：

Chen, Xiaolu ^{[1
]}

Liu, Yanan ^{[1
]}

Zhang, Liting ^{[1
]}

Chen, Daoxing ^{[1
]}

Dong, Zhaojun ^{[1
]}

Zhao, Chengguang ^{[1
]}

Liu, Zhiguo ^{[1
]}

Xia, Qinqin ^{[1
]}

Wu, Jianzhang ^{[1
]}

Chen, Yongheng ^{[2
,3
,4
,5
]}

Zheng, Xiaohui ^{[1
]}

Cai, Yuepiao ^{[1
]}

机构：

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China

[2] Cent South Univ, Xiangya Hosp, Dept Oncol, NHC Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China

[3] Cent South Univ, Xiangya Hosp, Lab Struct Biol, Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Hosp, Coll Life Sci, Changsha 410008, Hunan, Peoples R China

[5] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 214卷

基金：

中国国家自然科学基金;

关键词：

Indazole derivatives; Hepatocellular carcinoma; Fibroblast growth factor receptor 4; Covalent inhibitor; Antitumor activity;

D O I：

10.1016/j.ejmech.2021.113219

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fibroblast growth factor receptor 4 (FGFR4) is a member of the fibroblast growth factor receptor family, which is closely related to the occurrence and development of hepatocellular carcinoma (HCC). In this article, a series of indazole derivatives were designed and synthesized by using computer-aided drug design (CADD) and structure-based design strategies, and then they were evaluated for their inhibition of FGFR4 kinase and antitumor activity. F-30 was subtly selective for FGFR4 compared to FGFR1; it affected cell growth and migration by inhibiting FGFR4 pathways in HCC cell lines in a dose-dependent manner. (C) 2021 Elsevier Masson SAS. All rights reserved.

引用

页数：13

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