PLX3397

PLX3397, also known as pexidartinib, is a small-molecule tyrosine kinase inhibitor that selectively targets the colony-stimulating factor 1 receptor (CSF1R). CSF1R signaling drives the survival and proliferation of macrophages and microglia; by inhibiting CSF1R, PLX3397 reduces the number and activity of these cells in various tissues.

In preclinical research, PLX3397 is used to deplete tumor-associated macrophages and microglia to study their roles in cancer and neurodegenerative disease. It has been evaluated in models of glioblastoma, breast cancer, osteoarthritis, and other conditions, and is often used to modulate the tumor microenvironment or central nervous system inflammation, sometimes in combination with other therapies.

Clinically, PLX3397 was developed by Plexxikon and is marketed as pexidartinib (brand name Turalio) following regulatory approval. In 2019, pexidartinib received FDA approval for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitation, marking the first approval of a CSF1R inhibitor for this indication.

Safety and regulatory considerations: Pexidartinib is associated with hepatotoxicity and liver function abnormalities, and the FDA requires liver monitoring and includes a boxed warning for potential liver injury. Other common adverse events include fatigue, hair color changes, edema, and nausea. The drug is taken orally and is not suitable for all patients; dosing and monitoring are guided by regulatory labeling.