Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors
Staci L Haney1, Veronica S Wills2, David F Wiemer3
1Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. staci.haney@unmc.edu.
Abstract:
The enzyme geranylgeranyl diphosphate synthase (GGDPS) catalyzes the synthesis of the 20-carbon isoprenoid geranylgeranyl diphosphate (GGPP). GGPP is the isoprenoid donor for protein geranylgeranylation reactions catalyzed by the enzymes geranylgeranyl transferase (GGTase) I and II. Inhibitors of GGDPS result in diminution of protein geranylgeranylation through depletion of cellular GGPP levels, and there has been interest in GGDPS inhibitors as potential anti-cancer agents. Here we discuss recent advances in the development of GGDPS inhibitors, including insights gained by structure-function relationships, and review the preclinical data that support the continued development of this novel class of drugs.
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