tinlorafenib

Tinlorafenib (PF-07284890, ARRY-461) is an orally bioavailable, brain-penetrant small molecule inhibitor of BRAF and CRAF kinases. Developed by Pfizer (following the acquisition of Array BioPharma), it is specifically designed to target BRAF V600 mutations, including V600E and V600K, which drive the MAPK/ERK signaling pathway in various malignancies. A key differentiator for tinlorafenib is its ability to cross the blood-brain barrier; it is not a substrate for the human P-glycoprotein (P-gp) efflux transporter, allowing for significant central nervous system (CNS) exposure. This profile addresses a major limitation of earlier BRAF inhibitors, which often show poor brain penetration, leading to disease progression in the brain. Tinlorafenib is primarily being investigated for the treatment of BRAF V600-mutant solid tumors, particularly metastatic melanoma with brain involvement, both as a monotherapy and in combination with MEK inhibitors like binimetinib.