Fulzerasib is a KRAS G12C inhibitor. Inhibits the growth of KRAS G12C mutant tumor cell lines (IC50=2-20 nM). It can be used for the treatment of non-small cell lung cancer.

Fulzerasib is an irreversible small molecule inhibitor for KRAS G12C mutation blocking KRAS pathway signaling (pERK IC50: 37 nM) by covalently inhibiting the GDP/GTP nucleotide exchange on KRAS G12C (IC50: 29 nM), trapping KRAS in the inactive GDP-bound form (RAS-GTP IC50: 74 nM), and therefore inhibits the growth of KRAS G12C-mutant tumor cell lines (IC50: 2-20 nM). [1]

Fulzerasib also demonstrated potent anti-tumor activity in multiple KRAS G12C-mutant tumor models including MIA Paca-2 CDX, human lung adenocarcinoma NCI-H358 CDX, colorectal adenocarcinoma SW837 CDX, and lung cancer LU2529 PDX models, with minimum effective doses of 1 mg/kg, 3 mg/kg, 10 mg/kg and 2 mg/kg, respectively. [1]