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Molecules 2017, 22(6), 886; doi:10.3390/molecules22060886

Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

1
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Robert M. Coates
Received: 4 April 2017 / Revised: 24 May 2017 / Accepted: 24 May 2017 / Published: 27 May 2017
(This article belongs to the Special Issue Isoprenoid Biosynthesis)
View Full-Text   |   Download PDF [1171 KB, uploaded 27 May 2017]   |  

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. View Full-Text
Keywords: geranylgeranyl diphosphate synthase; isoprenoid; geranylgeranylation; inhibitors geranylgeranyl diphosphate synthase; isoprenoid; geranylgeranylation; inhibitors
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Haney, S.L.; Wills, V.S.; Wiemer, D.F.; Holstein, S.A. Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors. Molecules 2017, 22, 886.

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