Pemigatinib’s mechanism of action

Pemigatinib (Pemigatinib) is a small molecule kinase inhibitor that acts on FGFR1, 2 and 3 with IC50 value less than 2nM. By activating FGFR amplification and fusion, leading to constitutive activation of FGFR signaling, pemetinib inhibits FGFR1-3 phosphorylation and signaling and reduces cell viability in cancer cell lines. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Pemetinib showed antitumor activity in mouse xenograft models of human tumors in which alterations in FGFR1, FGFR2, or FGFR3 resulted in constitutive FGFR activation, including a cholangiocarcinoma patient xenograft model expressing an oncogenic FGFR2-Transformer-2β homolog (TRA2b) fusion protein and a KG1 leukemia model harboring an FGFR1 translocation (FGFR1OP2-FGFR1).