A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration

被引：10

作者：

Wu, Jianzhang ^{[1
]}

Du, Xiaojing ^{[2
]}

Li, Wulan ^{[1
,3
]}

Zhou, Yangyang ^{[1
,2
]}

Bai, Encheng ^{[1
,2
]}

Kang, Yanting ^{[1
,2
]}

Chen, Qiuxiang ^{[1
,2
]}

Fu, Weitao ^{[1
]}

Yun, Di ^{[1
]}

Xu, Qing ^{[4
]}

Qiu, Peihong ^{[1
]}

Jin, Rong ^{[2
,5
]}

Cai, Yuepiao ^{[1
]}

Liang, Guang ^{[1
]}

机构：

[1] Wenzhou Med Univ, Coll Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Digest Dis, Wenzhou 325000, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Coll Informat Sci & Comp Engn, Clin Med Coll 1, Wenzhou 325035, Zhejiang, Peoples R China

[4] Wenzhou Univ, Coll Chem & Mat Engn, Wenzhou 325035, Zhejiang, Peoples R China

[5] Wenzhou Med Univ, Affiliated Hosp 1, Dept Epidemiol, Wenzhou 325000, Zhejiang, Peoples R China

来源：

APOPTOSIS | 2017年 / 22卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Gastric cancer; Non-ATP competitive FGFR1 inhibitor; Proliferation; Survival; Migration; FACTOR RECEPTOR 1; GROWTH-FACTOR RECEPTORS; GENE AMPLIFICATION; LUNG-CANCER; DISCOVERY; EXPRESSION; TARGET;

D O I：

10.1007/s10495-017-1361-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activity in a gastric cancer xenograft tumor model by targeting FGFR1 signaling. These results show that L16H50 is a potent non-ATP-competitive FGFR1 inhibitor and may provide strong rationale for its evaluation in gastric cancer patients.

引用

页码：852 / 864

页数：13

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