FGFR2 Kinase Domain in Complex with a Pyrazolo[1,5-a]pyrimidine Analog (Compound 29)

Description: This structure elucidates the binding mode of Compound 29, a potent and selective FGFR2/3 inhibitor that retains low-nanomolar potency against common gatekeeper mutants. The structure was instrumental in guiding SAR optimization to achieve excellent selectivity over FGFR1, addressing treatment-related resistance mechanisms in cholangiocarcinoma and bladder cancer.