Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

被引：27

作者：

Haney, Staci L. ^{[1
]}

Wills, Veronica S. ^{[2
]}

Wiemer, David F. ^{[2
]}

Holstein, Sarah A. ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA

[2] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA

来源：

MOLECULES | 2017年 / 22卷 / 06期

基金：

美国国家卫生研究院;

关键词：

geranylgeranyl diphosphate synthase; isoprenoid; geranylgeranylation; inhibitors; NITROGEN-CONTAINING BISPHOSPHONATES; MULTIPLE-MYELOMA CELLS; ISOPRENOID BISPHOSPHONATES; TRIAZOLE BISPHOSPHONATES; PYROPHOSPHATE SYNTHASE; REDUCTASE INHIBITORS; MEVALONATE PATHWAY; PROTEIN PRENYLATION; BONE-RESORPTION; LOVASTATIN;

D O I：

10.3390/molecules22060886

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：12

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