哺乳动物香叶基香叶基二磷酸合酶抑制剂开发的最新进展
Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors.
作者信息
Haney Staci L, Wills Veronica S, Wiemer David F, Holstein Sarah A
机构信息
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA.
出版信息
Molecules. 2017 May 27;22(6):886. doi: 10.3390/molecules22060886.
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.
香叶基香叶基二磷酸合酶（GGDPS）催化20碳类异戊二烯香叶基香叶基二磷酸（GGPP）的合成。GGPP是由香叶基香叶基转移酶（GGTase）I和II催化的蛋白质香叶基香叶基化反应的类异戊二烯供体。GGDPS抑制剂通过降低细胞内GGPP水平导致蛋白质香叶基香叶基化减少，并且人们对GGDPS抑制剂作为潜在的抗癌药物很感兴趣。在此，我们讨论GGDPS抑制剂开发的最新进展，包括通过结构-功能关系获得的见解，并回顾支持这类新型药物持续开发的临床前数据。
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