Abstract
Over the last fifteen years there has been much excitement in the idea that targeting phosphodiesterase (PDE) 4 with small molecule inhibitors could lead to the discovery of novel, steroid-sparing compounds with utility in treating a multitude of diseases associated with chronic inflammation. However, dose-limiting side effects, of which nausea and vomiting are the most common are worrisome, have hampered their clinical development. Indeed, a fundamental obstacle that still is to be overcome by the pharmaceutical industry is to make compounds that dissociate beneficial from the adverse events. Unfortunately, both of these activities of PDE4 inhibitors represents an extension of their pharmacology and improving the therapeutic ratio has proved to be a major challenge. Several strategies have been considered, with some degree of success, but compounds with an optimal pharmacophore still have not been reported. An alternative approach to targeting PDE4 is to inhibit other cAMP PDE families that are also expressed in immune and pro-inflammatory cells in the hope that the beneficial activity can be retained at the expense of side effects. One such candidate is PDE7A. In this article we review the literature on PDE7A and explore the possibility that selective small molecule inhibitors of this enzyme family could provide a novel approach to alleviate the inflammation that is associated with many inflammatory diseases including asthma, chronic obstructive pulmonary disease, atopic dermatitis, psoriasis, lupus, rheumatoid arthritis and multiple sclerosis.
Keywords: cAMP, phosphodiesterase 7, chronic inflammation, therapeutic target, asthma, COPD
Current Pharmaceutical Design
Title: Phosphodiesterase 7A: A New Therapeutic Target for Alleviating Chronic Inflammation?
Volume: 12 Issue: 25
Author(s): M. A. Giembycz and S. J. Smith
Affiliation:
Keywords: cAMP, phosphodiesterase 7, chronic inflammation, therapeutic target, asthma, COPD
Abstract: Over the last fifteen years there has been much excitement in the idea that targeting phosphodiesterase (PDE) 4 with small molecule inhibitors could lead to the discovery of novel, steroid-sparing compounds with utility in treating a multitude of diseases associated with chronic inflammation. However, dose-limiting side effects, of which nausea and vomiting are the most common are worrisome, have hampered their clinical development. Indeed, a fundamental obstacle that still is to be overcome by the pharmaceutical industry is to make compounds that dissociate beneficial from the adverse events. Unfortunately, both of these activities of PDE4 inhibitors represents an extension of their pharmacology and improving the therapeutic ratio has proved to be a major challenge. Several strategies have been considered, with some degree of success, but compounds with an optimal pharmacophore still have not been reported. An alternative approach to targeting PDE4 is to inhibit other cAMP PDE families that are also expressed in immune and pro-inflammatory cells in the hope that the beneficial activity can be retained at the expense of side effects. One such candidate is PDE7A. In this article we review the literature on PDE7A and explore the possibility that selective small molecule inhibitors of this enzyme family could provide a novel approach to alleviate the inflammation that is associated with many inflammatory diseases including asthma, chronic obstructive pulmonary disease, atopic dermatitis, psoriasis, lupus, rheumatoid arthritis and multiple sclerosis.
Export Options
About this article
Cite this article as:
Giembycz A. M. and Smith J. S., Phosphodiesterase 7A: A New Therapeutic Target for Alleviating Chronic Inflammation?, Current Pharmaceutical Design 2006; 12 (25) . https://dx.doi.org/10.2174/138161206778194123
DOI https://dx.doi.org/10.2174/138161206778194123 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Tregs in Cancer: Foxp3 as a Putative Target for Therapy
Current Signal Transduction Therapy Hypoxia Upregulates MAPK<sup>p38</sup>/MAPK<sup>ERK</sup> Phosphorylation In Vitro: Neuroimmunological Differential Time-Dependent Expression of MAPKs
Protein & Peptide Letters Recent Advances in the Imaging of Programmed Cell Death
Current Pharmaceutical Design The Use of Structural Biology in Janus Kinase Targeted Drug Discovery
Current Drug Targets TNF-Related Apoptosis-Inducing Ligand (TRAIL) as a Pro-Apoptotic Signal Transducer with Cancer Therapeutic Potential
Current Pharmaceutical Design Pleuroparenchymal Fibroelastosis: Its Clinical Characteristics
Current Respiratory Medicine Reviews Protective Effects of Curcumin Against Nephrotoxic Agents
Cardiovascular & Hematological Disorders-Drug Targets Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance
Current Topics in Medicinal Chemistry Cell Immunity in Coronary Artery Disease (CAD)
Current Immunology Reviews (Discontinued) The Heme Oxygenase System and Type-1 Diabetes
Current Pharmaceutical Design In vitro & in vivo Studies on Lornoxicam Loaded Nanoemulsion Gels for Topical Application
Current Drug Delivery Albumin-Based Nanodevices as Drug Carriers
Current Pharmaceutical Design Molecular Phenotype of CXCL12β 3UTR G801A Polymorphism (rs1801157) Associated to HIV-1 Disease Progression
Current HIV Research Emerging Roles of MicroRNA-22 in Human Disease and Normal Physiology
Current Molecular Medicine Hypersensitivity Pneumonitis
Current Pediatric Reviews Inhibition of Lysozyme by Taurine Dibromamine
Protein & Peptide Letters Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Intraarticular Application of Unsealed Beta-Emitting Radionuclides in the Treatment Course of Inflammatory Joint Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Temporal Relationship between Pain Intensity and Pain Interference and Incident Dementia
Current Alzheimer Research Lipid Lowering Agents and the Endothelium: An Update after 4 Years
Current Vascular Pharmacology