title: Advances in targeting cyclic nucleotide phosphodiesterases.
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.
authors.affiliation: Biomedical and Molecular Sciences, Queen's University, Kingston K7L3N6, Ontario, Canada.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Maurice
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Hengming
authors.initials: H
authors.lastname: Ke
authors.affiliation: Cardiovascular and Pulmonary Branch, The National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Beijing Technology and Business University, Beijing 100048, China.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Genetics and Developmental Biology Center, The National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Chung
authors.affiliation: Cardiovascular and Pulmonary Branch, The National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Manganiello
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP