A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration.
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.
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.
Jianzhang
J
Wu
Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Xiaojing
X
Du
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.|College of Information Science and Computer Engineering, the First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Wulan
W
Li
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.|Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Yangyang
Y
Zhou
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.|Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Encheng
E
Bai
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.|Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Yanting
Y
Kang
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.|Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Qiuxiang
Q
Chen
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.
Weitao
W
Fu
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.
Di
D
Yun
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325035, China.
Qing
Q
Xu
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China. wjzwzmc@126.com.
Peihong
P
Qiu
Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. jinrongjrjr@163.com.|Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. jinrongjrjr@163.com.
Rong
R
Jin
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China. ypcai@126.com.
Yuepiao
Y
Cai
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China.
Guang
G
Liang
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D006843:Hydrocarbons, Chlorinated; C000626208:L16H50; D000255:Adenosine Triphosphate; D051496:Receptor, Fibroblast Growth Factor, Type 1
Gastric cancer; Migration; Non-ATP competitive FGFR1 inhibitor; Proliferation; Survival