In this article, we will discuss Pexidartinib (Mechanism of Action). So, let’s get started.
Mechanism of Action
Pexidartinib is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. In vitro, pexidartinib inhibited proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R. Pexidartinib also inhibited the proliferation of a CSF1R dependent cell line in vivo.
There is an exposure response relationship between pexidartinib steady state exposure
and serum transaminase levels (ALT and AST) with a higher risk of increased serum
transaminases at higher exposure. Additionally, increased transaminases occurred more frequently with higher pexidartinib doses (200 to 1200 mg per day).
At two times the mean maximum exposure of the 400 mg twice daily dose, pexidartinib
does not prolong the QTc interval to any clinically relevant extent.