PF-07799933

PF-07799933 is an orally bioavailable, selective ATP-competitive small-molecule inhibitor of RAF kinases, specifically targeting BRAF Class I (V600-mutant), Class II (dimeric mutations), and Class III (loss-of-function mutations that transactivate wildtype BRAF heterodimers). Developed by Pfizer, it is designed to suppress the RAF/MEK/ERK signaling pathway in tumor cells with both V600 and non-V600 BRAF alterations. Unlike approved class I BRAF inhibitors, PF-07799933 demonstrates activity against dimeric forms of mutant BRAF and shows significantly less paradoxical activation. It has shown anti-tumor activity in preclinical models as monotherapy and in combination with other targeted agents such as binimetinib or cetuximab. The compound is also believed to be brain penetrant, addressing a key limitation of earlier generation inhibitors[1][4][5][6][7].