[CAS NO. 1629268-00-3]  ARS-853

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% (IC ₅₀ ) of 2.5 μM, which is similar to its IC ₅₀ 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] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.