MRTX0902

MRTX0902 is a potent, selective, orally bioavailable, and brain-penetrant small molecule inhibitor of Son of Sevenless 1 (SOS1), developed to disrupt the protein-protein interaction between SOS1 and KRAS. By binding to SOS1, it prevents the activation of KRAS by blocking its interaction with GDP-bound (inactive) KRAS. This inhibition targets RAS-MAPK pathway signaling and is being investigated for use in advanced solid tumors harboring mutations in the KRAS MAPK pathway—including those with mutations in KRAS, NF1, PTPN11, SOS1 itself, class III BRAF, or EGFR. Preclinical studies have shown that MRTX0902 can inhibit tumor growth both as a single agent and in combination with other targeted therapies such as adagrasib (KRAS G12C inhibitor) or avutometinib (RAF/MEK clamp). The drug was originally developed by Mirati Therapeutics and is now under Bristol Myers Squibb following acquisition[1][2][5][6][7].