Structural insights into the potency and selectivity of covalent pan-FGFR inhibitors

Abstract

The human fibroblast growth factor receptors (FGFRs) are attractive targets for cancer therapy, but the structural basis for kinase targeting and gatekeeper mutations of covalent FGFR inhibitors are not fully understood. Here the authors report and discuss the potency and selectivity of FGFR inhibitors FIIN-2, TAS-120 and PRN1371 based on the co-crystal structures of SRC/FIIN-2, SRC/TAS-120 and FGFR4/PRN1371 complexes.