covalent NRAS inhibitor

Covalent NRAS inhibitors are preclinical-stage small molecules designed to selectively and covalently bind to the palmitoylation site (specifically cysteine 181, or C181) of the GTPase NRas. Palmitoylation is a critical post-translational modification required for NRAS trafficking, membrane localization, and downstream oncogenic signaling. By covalently modifying C181, these inhibitors prevent NRAS palmitoylation and subsequent membrane anchoring, thereby blocking NRAS-driven oncogenic pathways. Covant Therapeutics is actively developing these covalent NRAS inhibitors for the treatment of NRAS-mutant cancers, such as melanoma and acute myeloid leukemia (AML), demonstrating selective growth inhibition in mutant NRAS-driven cell lines.

Other names

NRAS Inhibitor (Covant)