Geranylgeranyl diphosphate is a 20-carbon isoprenoid phospholipid whose lipid moiety can be post-translationally incorporated into proteins to promote membrane association. The process of geranylgeranylation has been implicated in anti-proliferative effects of clinical agents that inhibit enzymes of the mevalonate pathway (i.e. statins and nitrogenous bisphosphonates) as well as experimental agents that deplete geranylgeranyl diphosphate. Inhibitors of geranylgeranyl diphosphate synthase are an attractive way to block geranylgeranylation because they possess a calcium-chelating substructure to allow localization to bone and take advantage of a unique position of the enzyme within the biosynthetic pathway. Here, we describe recent advances in geranylgeranyl diphosphate synthase expression and inhibitor development with a particular focus on the molecular mechanisms that link geranylgeranyl diphosphate to cell proliferation via geranylgeranylated small GTPases.

Geranylgeranyl diphosphate是20碳的类异戊二烯磷脂，其脂质部分可以翻译后整合到蛋白质中，以促进膜缔合。香叶基香叶基的酰化过程与抑制甲羟戊酸途径的酶的临床药物（即他汀类和双膦酸氮）以及消耗香叶基香叶基二磷酸的实验药物的抗增殖作用有关。香叶基香叶基二磷酸合酶的抑制剂是阻止香叶基香叶基化的一种有吸引力的方法，因为它们具有钙螯合的亚结构，可以定位于骨骼并利用酶在生物合成途径中的独特位置。这里，