In this article, we will discuss Pemigatinib (Mechanism of Action). So, let’s get started.
Mechanism of Action
Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2 Transformer-2 beta homolog (TRA2b) fusion protein.
Pharmacodynamics
Cardiac Electrophysiology
At a dose 1.5 times the maximum recommended dose, Pemigatinib does not result in a large mean increase (i.e. >20 ms) of the QTc interval.
Serum Phosphate
Pemigatinib increased serum phosphate levels as a consequence of FGFR inhibition. In patients, the increase in serum phosphate observed after treatment with pemigatinib was exposure-dependent across the dose range of 1 to 20 mg once daily (0.07 to 1.5 times the recommended dose), with increased risk of hyperphosphatemia with higher pemigatinib exposure.