MRTX0920

MRTX0920 is a potent, selective, and orally bioavailable small molecule inhibitor of Son of Sevenless homolog 1 (SOS1), a guanine nucleotide exchange factor (GEF) that plays a critical role in the activation of RAS proteins. Developed by Mirati Therapeutics (now a subsidiary of Bristol Myers Squibb), MRTX0920 works by binding to SOS1 and preventing the exchange of GDP for GTP on KRAS, thereby maintaining KRAS in its inactive "off" state. This mechanism effectively disrupts the RAS/MAPK signaling pathway, which is a major driver of tumor growth and survival in various cancers. MRTX0920 has demonstrated significant preclinical activity, particularly in combination with KRAS G12C inhibitors like adagrasib, where it helps to overcome adaptive resistance and feedback-mediated reactivation of the MAPK pathway. It is currently being evaluated in the preclinical and IND-enabling stages for the treatment of KRAS-mutant solid tumors.