Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

Staci L Haney; Veronica S Wills; David F Wiemer; Sarah A Holstein

doi:10.3390/molecules22060886

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Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

Journal article

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Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

Staci L Haney, Veronica S Wills, David F Wiemer and Sarah A Holstein

Molecules (Basel, Switzerland), Vol.22(6), p.886

05/27/2017

DOI: 10.3390/molecules22060886

PMCID: PMC5902023

PMID: 28555000

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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.

Terpenes - pharmacology

Farnesyltranstransferase - metabolism

Protein Prenylation - drug effects

Terpenes - chemistry

Animals

Enzyme Inhibitors - chemistry

Humans

Enzyme Inhibitors - pharmacology

Farnesyltranstransferase - antagonists & inhibitors

Structure-Activity Relationship

Details

Title: Subtitle: Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors
Creators: Staci L Haney - Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. staci.haney@unmc.edu
Veronica S Wills - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA. vwills87@gmail.com
David F Wiemer - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA. david-wiemer@uiowa.edu
Sarah A Holstein - Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. sarah.holstein@unmc.edu
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.22(6), p.886
DOI: 10.3390/molecules22060886
PMID: 28555000
PMCID: PMC5902023
NLM abbreviation: Molecules
ISSN: 1420-3049
eISSN: 1420-3049
Publisher: Switzerland
Grant note: T32 GM008365 / NIGMS NIH HHS R01 CA172070 / NCI NIH HHS
Language: English
Date published: 05/27/2017
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9983985832902771

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