Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor

Aberrant
activation of FGFR has been linked to the pathogenesis
of many tumor types. Selective inhibition of FGFR has emerged as a
promising approach for cancer treatment. Herein, we describe the discovery
of compound 38 (INCB054828, pemigatinib), a highly potent
and selective inhibitor of FGFR1, FGFR2, and FGFR3 with excellent
physiochemical properties and pharmacokinetic profiles. Pemigatinib
has received accelerated approval from the U.S. Food and Drug Administration
for the treatment of adults with previously treated, unresectable
locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion
or other rearrangement. Additional clinical trials are ongoing to
evaluate pemigatinib in patients with FGFR alterations.