Farnesylation involves the utilization of farnesyl pyrophosphate (FPP), an intermediate in the mevalonate pathway, by farnesyltransferase (FTase) to add a lipid, farnesyl, to certain proteins. This post-translational modification is crucial in allowing target proteins, including Ras, to associate with, and function at, membranes. FTase Inhibitor II is a cell-permeable analog of FPP that potently inhibits FTase (IC50 = 50-75 nM), preventing farnesylation of Ras. It does not inhibit geranylgeranyl transferase at similar concentrations (IC50 > 100 μM). FTase Inhibitor II displays no toxicity to untransformed cells but blocks Ras-mediated transformation of NIH 3T3 cells.
