ARS-853

ARS-853 is a cell-active, selective, covalent KRAS G12C inhibitor with an IC₅₀ of 2.5 μM. ARS-853 inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation^[1][2]. IC50 & Target: IC50: 2.5 μM (KRAS^G12C)^[1] In Vitro: ARS853 is designed to bind KRAS^G12C with high affinity. Treatment of KRAS^G12C-mutant lung cancer cells with ARS853 reduces the level of GTP-bound KRAS by more than 95% (10 μM). ARS853 inhibits proliferation with an inhibitory concentration 50% (IC₅₀) of 2.5 μM, which is similar to its IC₅₀ for target inhibition. ARS853 (10 μM) inhibits effector signaling and cell proliferation to varying degrees in six KRAS^G12C mutant lung cancer cell lines, but not in non-KRAS^G12C models. Similarly, it completely suppresses the effects of exogenous KRAS^G12C expression on KRAS-GTP levels, KRAS-BRAF interaction, and ERK signaling. ARS-853 treatment also induces apoptosis in four KRAS^G12C mutant cell lines. ARS853 selectively reduces KRAS-GTP levels and RAS-effector signaling in KRAS^G12C-mutant cells, while inhibiting their proliferation and inducing cell death^[1]. ARS-853 inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation^[2].