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.
IC50&Target
KRAS(G12C)
2.5 μM (IC50)
体外研究
ARS853 is designed to bind KRAS with high affinity. Treatment of KRAS-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 mutant lung cancer cell lines, but not in non-KRAS models. Similarly, it completely suppresses the effects of exogenous KRAS expression on KRAS-GTP levels, KRAS-BRAF interaction, and ERK signaling. ARS-853 treatment also induces apoptosis in four KRAS mutant cell lines. ARS853 selectively reduces KRAS-GTP levels and RAS-effector signaling in KRAS-mutant cells, while inhibiting their proliferation and inducing cell death. ARS-853 inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation.
分子式
C22H29ClN4O3
分子量
432.94
CAS号
1629268-00-3
运输条件
Room temperature in continental US; may vary elsewhere.