Dysregulation of isoprenoid biosynthesis is implicated in numerous biochemical disorders that play a role in the onset and/or progression of age-related diseases, such as hypercholesterolemia, osteoporosis, various cancers, and neurodegeneration. The mevalonate metabolic pathway is responsible for the biosynthesis of the two key isoprenoid metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational prenylation of various proteins, including the small GTP-binding proteins (GTPases), with either FPP or GGPP is vital for proper localization and activation of these proteins. Prenylated GTPases play a critical role in cell signaling, proliferation, cellular plasticity, oncogenesis, and cancer metastasis. Pre-clinical and clinical studies strongly suggest that inhibition of protein prenylation can be an effective treatment for non-skeletal cancers. In this review, we summarize the most recent drug discovery efforts focusing on blocking protein farnesylation and/or geranylgeranylation and the biochemical and structural data available in guiding the current on-going studies in drug discovery. Furthermore, we provide a summary on the biochemical association between disruption of protein prenylation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR) signaling, and cancer.

类异戊二烯生物合成的失调涉及许多生化疾病，这些疾病在与年龄有关的疾病（例如高胆固醇血症，骨质疏松症，各种癌症和神经变性）的发作和/或进展中起作用。甲羟戊酸代谢途径负责两个关键的类异戊二烯代谢物，焦磷酸法呢基（FPP）和香叶基香叶基香叶基（GGPP）的生物合成。用FPP或GGPP将包括小GTP结合蛋白（GTPases）在内的各种蛋白质进行翻译后异戊二烯化对于正确定位和激活这些蛋白质至关重要。烯丙基化的GTPases在细胞信号传导，增殖，细胞可塑性，肿瘤发生和癌症转移中起关键作用。临床前和临床研究强烈表明，抑制蛋白质异戊二烯酸酯可以有效治疗非骨骼癌。在这篇综述中，我们总结了最近的药物发现工作，重点是阻断蛋白质法呢基化和/或香叶基香叶基化，以及可用于指导当前正在进行的药物研究的生化和结构数据。此外，我们提供了蛋白质异戊二烯化的破坏，内质网（ER）应激，未折叠的蛋白质反应（UPR）信号传导和癌症之间的生化联系的摘要。我们总结了最近的药物发现工作，重点是阻断蛋白质的法呢基化和/或香叶基香叶基化，以及可用于指导当前正在进行的药物研究的生化和结构数据。此外，我们提供了蛋白质异戊二烯化的破坏，内质网（ER）应激，未折叠的蛋白质反应（UPR）信号传导和癌症之间的生化联系的摘要。我们总结了最近的药物发现工作，重点是阻断蛋白质的法呢基化和/或香叶基香叶基化，以及可用于指导当前正在进行的药物研究的生化和结构数据。此外，我们提供了蛋白质异戊二烯化的破坏，内质网（ER）应激，未折叠的蛋白质反应（UPR）信号传导和癌症之间的生化联系的摘要。