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Structure-Based Discovery of PDEs Inhibitors

[ Vol. 16 , Issue. 9 ]


Li Li, Wuyan Chen, Tiantian Chen, Jing Ren and Yechun Xu   Pages 917 - 933 ( 17 )


Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby regulating the cyclic nucleotide signalling pathways and biological responses. PDEs inhibitors can be used clinically for treatment of several diseases including central nervous system disorders, erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, and inflammatory diseases such as chronic obstructive pulmonary disease. However, the unfavourable risk-benefit ratio and side-effect profiles of non-selective PDEs inhibitors have impeded their therapeutic success and therefore spurred the pharmaceutical industry to develop family-selective PDE inhibitors. Given the recent remarkable advances in structure-based drug design, this review will summarize developments and achievements in structure-based search, design and optimization of PDEs inhibitors, and highlight the challenges that need to be addressed.


Crystal structure, Cyclic nucleotide signalling pathway, Family-selective inhibitor, Medicinal chemistry, Phosphodiesterases, Structure-based drug design.


CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, China.

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