Format

Send to

Choose Destination
Nat Rev Drug Discov. 2014 Apr;13(4):290-314. doi: 10.1038/nrd4228.

Advances in targeting cyclic nucleotide phosphodiesterases.

Author information

1
Biomedical and Molecular Sciences, Queen's University, Kingston K7L3N6, Ontario, Canada.
2
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
3
Cardiovascular and Pulmonary Branch, The National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
4
Beijing Technology and Business University, Beijing 100048, China.
5
Genetics and Developmental Biology Center, The National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

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.

PMID:
24687066
PMCID:
PMC4155750
DOI:
10.1038/nrd4228
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center