Phosphonates and bisphosphonates have proven their pharmacological utility as inhibitors of enzymes that metabolize phosphate and pyrophosphate substrates. The blockbuster class of drugs nitrogen-containing bisphosphonates represent one of the best-known examples. Widely used to treat bone-resorption disorders, these drugs work by inhibiting the enzyme farnesyl pyrophosphate synthase. Playing a key role in the isoprenoid biosynthetic pathway, this enzyme is also a potential anticancer target. Here, we provide a comprehensive overview of the research efforts to identify new inhibitors of farnesyl pyrophosphate synthase for various therapeutic applications. While the majority of these efforts have been directed against the human enzyme, some have been targeted on its homologs from other organisms, such as protozoan parasites and insects. Our particular focus is on the structures of the target enzymes and how the structural information has guided the drug discovery efforts.

膦酸酯和双膦酸酯已证明具有药理作用，可作为代谢磷酸盐和焦磷酸盐底物的酶的抑制剂。含氮双膦酸盐类药物的重磅炸弹代表了最著名的例子之一。这些药物广泛用于治疗骨吸收疾病，可通过抑制法呢基焦磷酸合酶来发挥作用。在类异戊二烯的生物合成途径中起关键作用，该酶也是潜在的抗癌靶标。在这里，我们提供了研究工作的全面概述，以鉴定用于各种治疗应用的法呢基焦磷酸合酶的新抑制剂。尽管这些努力中的大多数是针对人的酶，但也有一些人针对其他生物体的同源物，例如原生动物寄生虫和昆虫。