Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 13, Issue 4, Pages 290-314Publisher
NATURE PORTFOLIO
DOI: 10.1038/nrd4228
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Funding
- National Heart, Lung and Blood Institute (NHLBI) Intramural research Program at the US National Institutes of Health (NIH) in Bethesda, Maryland, USA
- Canadian Institutes of Health Research (CIHR)
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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.
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