Biomedical and Molecular Sciences, Queen's University, Kingston K7L3N6, Ontario, Canada.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Nat Rev Drug Discov. 2014 Apr;13(4):290-314. doi: 10.1038/nrd4228.
Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.
环核苷酸磷酸二酯酶（PDEs）催化环 AMP 和环 GMP 的水解，从而调节这些环核苷酸、它们的信号通路以及健康和疾病中无数生物反应的细胞内浓度。目前，临床上有少数 PDE 抑制剂用于治疗几种疾病中环核苷酸信号的病理生理失调，包括勃起功能障碍、肺动脉高压、急性难治性心力衰竭、间歇性跛行和慢性阻塞性肺疾病。然而，随着对特定 PDE 在调节特定环核苷酸信号通路的亚细胞区室化中的作用的认识不断加深，基于结构的新型特异性抑制剂的设计以及针对个体 PDE 变体的更复杂策略的发展，药物研发对 PDE 的兴趣重新燃起。
