ARS-1620

Description	ARS-1620 is a covalent compound with high potency and selectivity for KRAS-G12C.ARS-1620 selectively induces tumor regression in patient-derived tumor models. ARS-1620, an atropisomeric selective KRASG12C inhibitor with desirable PK. KRAS dependency is more profound in vivo compared to 2D-monolayer cell culture. ARS-1620 is a valuable pharmacological tool to interrogate KRAS biology in vivo. ARS-1620 achieves rapid and sustained in vivo target occupancy to induce tumor regression. We use ARS-1620 to dissect oncogenic KRAS dependency and demonstrate that monolayer culture formats significantly underestimate KRAS dependency in vivo. This study provides in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential.
Pathways	GPCR/G Protein
Targets	Ras/Rho

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