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

• Published in: Apoptosis (London) Vol. 22; no. 6; pp. 852 - 864
• Main Authors: Wu, Jianzhang, Du, Xiaojing, Li, Wulan, Zhou, Yangyang, Bai, Encheng, Kang, Yanting, Chen, Qiuxiang, Fu, Weitao, Yun, Di, Xu, Qing, Qiu, Peihong, Jin, Rong, Cai, Yuepiao, Liang, Guang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2017; Springer; Springer Nature B.V
• Subjects: Adenosine Triphosphate - metabolism; Animals; Antimitotic agents; Antineoplastic agents; Apoptosis - drug effects; ATP; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Care and treatment; Cell Biology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug therapy; Fibroblast growth factors; G2 Phase - drug effects; Health aspects; HEK293 Cells; Humans; Hydrocarbons, Chlorinated - chemistry; Hydrocarbons, Chlorinated - pharmacology; Hydrocarbons, Chlorinated - therapeutic use; Mice; Mitosis - drug effects; Oncology; Prevention; Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Signal Transduction - drug effects; Stomach cancer; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Tyrosine; Virology; Xenograft Model Antitumor Assays; Non-ATP competitive FGFR1 inhibitor; Proliferation; Gastric cancer; Survival; Migration
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-017-1361-7

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.