Article ID Journal Published Year Pages File Type
2112712 Cancer Letters 2014 8 Pages PDF
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.

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Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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