Therapeutic targeting of 3’,5’-cyclic nucleotide phosphodiesterases: inhibition and beyond

Baillie, G. S. , Tejeda, G. S. and Kelly, M. P. (2019) Therapeutic targeting of 3’,5’-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nature Reviews Drug Discovery, (doi:10.1038/s41573-019-0033-4) (PMID:31388135) (Early Online Publication)

Baillie, G. S. , Tejeda, G. S. and Kelly, M. P. (2019) Therapeutic targeting of 3’,5’-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nature Reviews Drug Discovery, (doi:10.1038/s41573-019-0033-4) (PMID:31388135) (Early Online Publication)

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Abstract

Phosphodiesterases (PDEs), enzymes that degrade 3′,5′-cyclic nucleotides, are being pursued as therapeutic targets for several diseases, including those affecting the nervous system, the cardiovascular system, fertility, immunity, cancer and metabolism. Clinical development programmes have focused exclusively on catalytic inhibition, which continues to be a strong focus of ongoing drug discovery efforts. However, emerging evidence supports novel strategies to therapeutically target PDE function, including enhancing catalytic activity, normalizing altered compartmentalization and modulating post-translational modifications, as well as the potential use of PDEs as disease biomarkers. Importantly, a more refined appreciation of the intramolecular mechanisms regulating PDE function and trafficking is emerging, making these pioneering drug discovery efforts tractable.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tejeda, Dr Rer Nat Gonzalo and Baillie, Professor George
Authors: Baillie, G. S., Tejeda, G. S., and Kelly, M. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Reviews Drug Discovery
Publisher:Nature Research
ISSN:1474-1776
ISSN (Online):1474-1784
Published Online:06 August 2019
Copyright Holders:Copyright © 2019 Springer Nature
First Published:First published in Nature Reviews Drug Discovery 2019
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
3014140Targeting PDE3/4 to allow regulation of cardiac calcium homeostasis in diseaseGeorge BaillieBritish Heart Foundation (BHF)PG/17/26/32881CAMS - Cardiovascular Science
660151Priming Innovative Translational Research - The University of Glasgow Confidence in Concept ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_13063RI CARDIOVASCULAR & MEDICAL SCIENCES
729861Priming Innovative Translational Research - the Glasgow Chemical Biology ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_15039RI CARDIOVASCULAR & MEDICAL SCIENCES