Inhibiting protein prenylation is an attractive means to modulate cellular processes
controlled by a variety of signaling proteins, including oncogenic proteins such as Ras and
Rho GTPases. The largest class of prenylated proteins contain a so-called CaaX motif at
their carboxyl termini and are subject to a maturation process initiated by the attachment of
an isoprenoid lipid by either protein farnesyltransferase (FTase) or protein
geranylgeranyltransferase type I (GGTase-I). Inhibitors of FTase, termed FTIs, have been the …