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.1,2 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.3 It does not inhibit geranylgeranyl transferase at similar concentrations (IC50 > 100 µM).3 FTase Inhibitor II displays no toxicity to untransformed cells but blocks Ras-mediated transformation of NIH 3T3 cells.3
1.Berndt, N., Hamilton, A.D., and Sebti, S.M.Targeting protein prenylation for cancer therapyNat. Rev. Cancer11(11)775-791(2011) 2.Appels, N.M.G.M., Beijnen, J.H., and Schellens, J.H.M.Development of farnesyl transferase inhibitors: A reviewOncologist10(8)565-578(2005) 3.Manne, V., Ricca, C.S., Brown, J.G., et al.Ras farnesylation as a target for novel antitumor agents: Potent and selective farnesyl diphosphate analog inhibitors of farnesyltransferaseDrug Dev. Res.34(2)121-137(1995)