ACE-47228211

ACE-47228211 is a highly potent, selective, and orally bioavailable small molecule inhibitor of Son of Sevenless homolog 1 (SOS1), developed by Acerand Therapeutics. SOS1 acts as a guanine nucleotide exchange factor (GEF) that catalyzes the conversion of KRAS from an inactive GDP-bound state to an active GTP-bound state. By disrupting the SOS1-KRAS protein-protein interaction, ACE-47228211 inhibits the activation of both wild-type and mutant KRAS (including G12D and G12C) and suppresses the reactivation of the RAS/MAPK signaling pathway. Preclinical data presented at AACR 2024 demonstrated that ACE-47228211 provides significant tumor growth inhibition in KRAS-mutant models and exhibits synergistic activity when combined with KRAS G12C, EGFR, or FGFR2 inhibitors. The compound is currently in the IND-enabling stage for the treatment of KRAS-MAPK driven cancers.