Fig. 4: Pemigatinib remains the excellent inhibitory efficacy for Val-to-Ile gatekeeper mutation but lower potency against Val-to-Met/Phe gatekeeper mutation.
From: Characterization of the cholangiocarcinoma drug pemigatinib against FGFR gatekeeper mutants
A Inhibitory effects of pemigatinib against FGFR1-3 gatekeeper mutants using kinase activity inhibition assays. B The collective half maximal inhibitory concentration (IC50) values for FGFR1-3 gatekeeper mutations summarized in detail. Error bars represent the standard deviation for at least three independent measurements. C–F Structural models of FGFR2 V564I/F, FGFR1 V561M and FGFR3 V555M in complex with pemigatinib. Pemigatinib colored cyan is from the binding models with the corresponding wild type where pemigatinib is docked into FGFR2 (PDB ID: 6LVL), and FGFR3 (PDB ID: 7DHL), and is aligned with the structural models of gatekeeper mutants. Pemigatinib colored orange is the predicted structure with gatekeeper mutants. The structural models of FGFR2 V564I/F, FGFR1 V561M and FGFR3 V555M in complex with pemigatinib are generated by substitution of gatekeeper residues on the basis of FGFR1 (PDB: 7WCL), FGFR2 (PDB: 6LVL) and FGFR3 (PDB: 7DHL) structures.
