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

Recent advances in the development of mammalian geranylgeranyl diphosphate synthase inhibitors

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

Research output: Contribution to journal › Review article › peer-review

19 Scopus citations

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.

Original language	English (US)
Article number	886
Journal	Molecules
Volume	22
Issue number	6
DOIs	https://doi.org/10.3390/molecules22060886
State	Published - Jun 2017

Keywords

Geranylgeranyl diphosphate synthase
Geranylgeranylation
Inhibitors
Isoprenoid

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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10.3390/molecules22060886

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title = "Recent advances in the development of mammalian geranylgeranyl diphosphate synthase inhibitors",

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.",

keywords = "Geranylgeranyl diphosphate synthase, Geranylgeranylation, Inhibitors, Isoprenoid",

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language = "English (US)",

volume = "22",

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AU - Haney, Staci L.

AU - Wills, Veronica S.

AU - Wiemer, David F.

AU - Holstein, Sarah A.

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N2 - 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.

AB - 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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KW - Geranylgeranylation

KW - Inhibitors

KW - Isoprenoid

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Recent advances in the development of mammalian geranylgeranyl diphosphate synthase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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