Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor
Liangxing Wu, Colin Zhang, Chunhong He, Ding‐Quan Qian, Liang Lü, Ya‐Ping Sun, Meizhong Xu, Jin‐Cong Zhuo, Phillip C.C. Liu, Ronald M. Klabe, Richard Wynn, Maryanne Covington, Karen Gallagher, Lynn Leffet, Kevin Bowman, Sharon Diamond, Holly K. Koblish, Yue Zhang, Maxim Soloviev, Gregory Hollis, Timothy C. Burn, Peggy Scherle, Swamy Yeleswaram, Reid Huber, Wenqing Yao
Abstract
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.