A cembranolide diterpene farnesyl protein transferase inhibitor from the marine soft coral Lobophytum cristagalli

A previously described cembranolide diterpene from Lobophytum cristagalli was identified as a potent (IC50 0.15 μM) inhibitor of farnesyl protein transferase (FPT). The compound showed selectivity for FPT as compared to the closely related enzyme geranylgeranyl protein transferase-1 (IC50 5.3 μM). Kinetic evaluation suggests that this compound competes with the protein/peptide farnesyl acceptor substrate, and not with farnesyl pyrophosphate for inhibition of FPT.