title: Discovery and identification of new non-ATP competitive FGFR1 inhibitors with therapeutic potential on non-small-cell lung cancer.
abstract: Fibroblast growth factor receptor (FGFR) tyrosine kinases have been regarded as a target for cancer treatment, and there is much interest in inhibiting FGF/FGFR signaling by small molecules as a therapeutic approach to cancer. Generally, inhibitors mimics ATP structure and block the binding between ATP and FGFR kinase. Here, two novel, non-ATP-competitive, selective, irreversible FGFR1 inhibitors, A114 and A117, were identified via kinase inhibitory assay from 156 synthetic bisaryl-1,4-dien-3-one derivatives. A "DFG-OUT" inactive conformation binding mode with FGFR1 was predicted by molecular docking. A114 and A117 showed significant anti-tumor activity both in vitro and in vivo via targeting FGFR1.
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Yi
authors: Y
authors: Wang
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Yuepiao
authors: Y
authors: Cai
authors: Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
authors: Jiansong
authors: J
authors: Ji
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Zhiguo
authors: Z
authors: Liu
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Chengguang
authors: C
authors: Zhao
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Yunjie
authors: Y
authors: Zhao
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Tao
authors: T
authors: Wei
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Xueqian
authors: X
authors: Shen
authors: Department of Pharmacy, The 1st Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Xiuhua
authors: X
authors: Zhang
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China. Electronic address: proflxk@163.com.
authors: Xiaokun
authors: X
authors: Li
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China. Electronic address: cuiliang1234@163.com.
authors: Guang
authors: G
authors: Liang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1