Phenolic replacements for cysteine in farnesyl transferase inhibitors based on CVFM

Compounds in which cysteine of the tetrapeptide CVFM has been replaced with a phenolic benzyl substituent inhibit farnesylation of H-ras protein by farnesyl transferase (FTase). In the most potent inhibitors (e.g., 5-chloro-2-hydroxybenzyl-VFM, IC₅₀ = 0.5 μM, approx. 8 times less active than CVFM) the phenolic hydroxyl is ortho to the methylene linker. Inhibitory activity is influenced by substitution on the phenol ring.