Inhibitors of phosphodiesterase as cancer therapeutics

• Published in: European journal of medicinal chemistry 2018-04, Vol.150, p.742-756
• Main Authors: Peng, Ting, Gong, Jun, Jin, Yongzhe, Zhou, Yanping, Tong, Rongsheng, Wei, Xin, Bai, Lan, Shi, Jianyou
• Format: Article
• Language: English
• Subjects: cAMP; Cancer; cGMP; Phosphodiesterase; Phosphodiesterase inhibitors
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.03.046

Phosphodiesterases (PDEs) are a class of enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which is involved in many physiological processes including visual transduction, cell proliferation and differentiation, cell-cycle regulation, gene expression, inflammation, apoptosis, and metabolic function. PDEs are composed of 11 different families and each family contains different subtypes. The distribution, expression, regulation mode and sensitivity to inhibitors of each subtype are different, and they are involved in cancer, inflammation, asthma, depression, erectile dysfunction and other pathological processes of development. A large number of studies have shown that PDEs play an important role in the development of tumors by affecting the intracellular level of cAMP and/or cGMP and PDEs could become diagnostic markers or therapeutic targets. This review will give a brief overview of the expression and regulation of PDE families in the process of tumorigenesis and their anti-tumor inhibitors, which may guide the design of novel therapeutic drugs targeting PDEs for anticancer agent. [Display omitted] •PDEs are composed of 11 different families and have different distribution, expression and regulation mode.•The PDEs are closely related to various cancer pathologies.•PDE inhibitors may be effective agents for treating cancer.•The structure-activity relationships of PDE inhibitors may guide the design of novel anti-tumor drugs.