ARS-853

Research use only, not for human use.

ARS-853 is a mutant-specific, covalent inhibitor of KRAS(G12C); engages KRASG12C in biochemical assay with a rate constant of 76 M-1s-1.

ARS-853 is a mutant-specific, covalent inhibitor of KRAS(G12C); engages KRASG12C in biochemical assay with a rate constant of 76 M-1s-1, > 600-fold improvement compared with Compound 12 (Ostrem JM, Nature 2013;503:548–51.); inhibits growth of H358 cells; the first direct KRAS inhibitor shown to selectively inhibit KRAS in cells with potency in the range of a drug candidate.

ARS853 is designed to bind KRASG12C with high affinity. Treatment of KRASG12C-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 KRASG12C mutant lung cancer cell lines, but not in non-KRASG12C models. Similarly, it completely suppresses the effects of exogenous KRASG12C expression on KRAS-GTP levels, KRAS-BRAF interaction, and ERK signaling. ARS-853 treatment also induces apoptosis in four KRASG12C mutant cell lines. ARS853 selectively reduces KRAS-GTP levels and RAS-effector signaling in KRASG12C-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.

——

ARS853 | ARS 853

MAPK/ERK Signaling

Ras

Ras

Cancer

——

1629268-00-3

432.9437

C22H29ClN4O3

>98% (HPLC)

DMSO: ≥ 71 mg/mL

C=CC(N1CC(N2CCN(C(CNC3=CC(C4(C)CC4)=C(Cl)C=C3O)=O)CC2)C1)=O

2-Propen-1-one, 1-[3-[4-[2-[[4-chloro-2-hydroxy-5-(1-methylcyclopropyl)phenyl]amino]acetyl]-1-piperazinyl]-1-azetidinyl]-

(-20℃)

With Ice Pack

≥ 2 years