Revolution Medicines has been developing variant inhibitors targeting SHP2, and RMC-4550 (91) (IC50 = 0.583 nM) is a potent and selective SHP2 inhibitor that has shown efficacy against human cancer models with RAS-GTP-dependent oncogenic BRAF, NF1 deletion, or nucleotide cycle oncogenic RAS (e.g., KRASG12C).289 RMC-4550 reduces oncogenic RAS/RAF/MEK/ERK signaling and cancer growth by disrupting SOS1-mediated RAS-GTP. The gene discussed is RAF1; the disease is cancer.