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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Structure-Based Discovery of PDEs Inhibitors

Author(s): Li Li, Wuyan Chen, Tiantian Chen, Jing Ren and Yechun Xu

Volume 16, Issue 9, 2016

Page: [917 - 933] Pages: 17

DOI: 10.2174/1568026615666150825142134

Price: $65


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.

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

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