ARS-1620

ARS-1620 is a first-in-class, potent, and highly selective small molecule inhibitor of the KRAS G12C mutant. It represents a landmark achievement in oncology as one of the first compounds to demonstrate that the KRAS protein, long considered "undruggable," could be effectively targeted by exploiting a previously hidden allosteric pocket (the switch II pocket) available in the inactive, GDP-bound state. ARS-1620 works by forming a covalent bond with the cysteine residue at position 12 of the mutant protein, effectively trapping it in its inactive conformation and preventing the activation of downstream oncogenic signaling pathways, such as the MAPK/ERK pathway. Developed by Wellspring Biosciences in collaboration with Araxes Pharma and Janssen, ARS-1620 served as a critical proof-of-concept molecule that validated KRAS G12C as a therapeutic target, paving the way for subsequent clinical-stage inhibitors like sotorasib and adagrasib. While ARS-1620 was primarily used as a preclinical lead and tool compound, its development led to the clinical candidate JNJ-74699157 (ARS-3248).

Other names

ARS 1620ARS1620ARS-1620