RMC-4998

RMC-4998 is a preclinical, orally active small molecule tri-complex inhibitor that selectively targets the active (GTP-bound) state of the KRAS G12C mutant protein. It works by forming a ternary complex with cyclophilin A (CYPA) and KRAS G12C, thereby inactivating oncogenic signaling driven by this mutation. This approach is designed to overcome resistance mechanisms seen with traditional KRAS G12C inhibitors that target the inactive (GDP-bound) state. Preclinical studies have demonstrated robust anti-tumor activity for RMC-4998 in models of KRAS G12C-mutant non-small cell lung cancer (NSCLC), both as monotherapy and in combination with other agents targeting different states of KRAS. The drug represents an innovative strategy to address "undruggable" cancer drivers by remodeling protein-protein interfaces[1][2][4][5].