MRTX849 (Adagrasib, MRTX-849) is a potent, selective, and covalent KRAS G12C inhibitor, inhibits KRAS-dependent signaling.
MRTX849 (Adagrasib) binds to, stabilizes and selectively modifies mutant cysteine 12 in GDP-bound KRAS G12C, and inhibits KRAS-dependent signaling.
MRTX849 (Adagrasib) inhibited KRAS-dependent signaling targets including ERK1/2 phosphorylation (Thr202/Tyr204 ERK1; pERK), S6 phosphorylation (RSK-dependent Ser235/236; pS6) and expression of the ERK-regulated DUSP6, each with IC50 values in the single-digit nanomolar range in KRASG12C-mutant H358 lung and MIA PaCa-2 pancreatic cancer cell lines.
MRTX849 (Adagrasib) potently inhibited cell growth in the vast majority of KRASG12C-mutant cell lines with IC50 of 10-973 nM.
MRTX849 (Adagrasib) inhibited KRAS signaling and tumor growth in vivo, demonstrated potent anti-tumor activity in KRASG12C-mutant and non KRASG12C-mutant human tumor xenografts models.