What is the target of pemetinib/pemetinib tablets?

Pemigatinib/Pemigatinib is a small molecule kinase inhibitor that exerts anti-tumor activity by inhibiting fibroblast growth factor receptor (FGFR). With an IC50 of less than 2nM, pemetinib exhibits potent inhibitory effects on FGFR1, FGFR2 and FGFR3. In mouse xenograft models of human tumors harboring FGFR1, 2, and 3 alterations, pemetinib demonstrated potent antitumor activity by inhibiting the growth of xenograft tumor models. It also showed efficacy in a patient-derived cholangiocarcinoma xenograft model expressing an oncogenic FGFR2 transformant 2β homolog (TRA2b) fusion protein. Pemetinib also inhibits FGFR4 in vitro, but at approximately 100 times the concentration that inhibits FGFR1, 2, and 3.5.

Pemetinib is a potent TKI targetingFGFR1-3 and rearranged forms such as FGFR3-TACC3 and FGFR2-TRA2B, and its anti-tumor activity has been demonstrated in genetically defined tumor models. Its clinical efficacy has been demonstrated in patients carrying FGFR mutations. In 2020, pemetinib was approved by the U.S. Food and Drug Administration (FDA) as the first targeted therapy for advanced cholangiocarcinoma, and in August 2022, it was approved for the treatment of relapsed or refractory myeloid/lymphoid tumors (MLNs) with FGFR1 rearrangements. To date, several ongoing clinical trials are evaluating pemetinib alone or in combination with other therapeutic agents in the treatment of various cancers. The trials include patients who have failed to respond to standard therapies or have FGFR mutations, including non-small cell lung cancer (NSCLC), bladder cancer, gastric cancer, colorectal cancer and glioma.