Abstract
Poly(ADP-ribose)polymerases (PARPs) catalyze a post-transcriptional modification of proteins, consisting in the attachment of mono, oligo or poly ADP-ribose units from NAD+ to specific polar residues of target proteins. The scientific interest in members of this superfamily of enzymes is continuously growing since they have been implicated in a range of diseases including stroke, cardiac ischemia, cancer, inflammation and diabetes.
Despite some inhibitors of PARP-1, the founder member of the superfamily, have advanced in clinical trials for cancer therapy, and other members of PARPs have recently been proposed as interesting drug targets, challenges exist in understanding the polypharmacology of current PARP inhibitors as well as developing highly selective chemical tools to unravel specific functions of each member of the superfamily.
Beginning with an overview on the molecular aspects that affect polypharmacology, in this article we discuss how these may have an impact on PARP research and drug discovery. Then, we review the most selective PARP inhibitors hitherto reported in literature, giving an update on the molecular aspects at the basis of selective PARP inhibitor design. Finally, some outlooks on current issues and future directions in this field of research are also provided.
Keywords: Cancer, drug design, poly(ADP-ribose)polymerases, polypharmacology, promiscuity, selective inhibitors, selectivity.
Current Topics in Medicinal Chemistry
Title:From Polypharmacology to Target Specificity: The Case of PARP Inhibitors
Volume: 13 Issue: 23
Author(s): Paride Liscio, Emidio Camaioni, Andrea Carotti, Roberto Pellicciari and Antonio Macchiarulo
Affiliation:
Keywords: Cancer, drug design, poly(ADP-ribose)polymerases, polypharmacology, promiscuity, selective inhibitors, selectivity.
Abstract: Poly(ADP-ribose)polymerases (PARPs) catalyze a post-transcriptional modification of proteins, consisting in the attachment of mono, oligo or poly ADP-ribose units from NAD+ to specific polar residues of target proteins. The scientific interest in members of this superfamily of enzymes is continuously growing since they have been implicated in a range of diseases including stroke, cardiac ischemia, cancer, inflammation and diabetes.
Despite some inhibitors of PARP-1, the founder member of the superfamily, have advanced in clinical trials for cancer therapy, and other members of PARPs have recently been proposed as interesting drug targets, challenges exist in understanding the polypharmacology of current PARP inhibitors as well as developing highly selective chemical tools to unravel specific functions of each member of the superfamily.
Beginning with an overview on the molecular aspects that affect polypharmacology, in this article we discuss how these may have an impact on PARP research and drug discovery. Then, we review the most selective PARP inhibitors hitherto reported in literature, giving an update on the molecular aspects at the basis of selective PARP inhibitor design. Finally, some outlooks on current issues and future directions in this field of research are also provided.
Export Options
About this article
Cite this article as:
Liscio Paride, Camaioni Emidio, Carotti Andrea, Pellicciari Roberto and Macchiarulo Antonio, From Polypharmacology to Target Specificity: The Case of PARP Inhibitors, Current Topics in Medicinal Chemistry 2013; 13 (23) . https://dx.doi.org/10.2174/15680266113136660209
DOI https://dx.doi.org/10.2174/15680266113136660209 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
From the Oxygen to the Organ Protection: Erythropoietin as Protagonist in Internal Medicine
Cardiovascular & Hematological Agents in Medicinal Chemistry Graphical Abstracts
Letters in Drug Design & Discovery Regression of Oxidative Stress by Targeting eNOS and Nrf2/ARE Signaling: A Guided Drug Target for Cardiovascular Diseases
Current Topics in Medicinal Chemistry Monocytes, Macrophages and Other Inflammatory Mediators of Abdominal Aortic Aneurysm
Current Pharmaceutical Design Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders
Current Neuropharmacology Hepatocyte Growth Factor (HGF) for a Cell-Signal-Based Therapy During Acute and Chronic Liver Diseases
Current Signal Transduction Therapy Hepatic Injury to the Newborn Liver Due to Drugs
Current Pharmaceutical Design Evolving Strategies in Manipulating VEGF/VEGFR Signaling for the Promotion of Angiogenesis in Ischemic Muscle
Current Pharmaceutical Design Protective Effect of GSK-3β/Nrf2 Mediated by Dimethyl Fumarate in Middle Cerebral Artery Embolization Reperfusion Rat Model
Current Neurovascular Research Toll-Like Receptor 4 Signaling Pathway as a Potential Targets for Stroke-Induced Inflammation
Current Signal Transduction Therapy Heat Shock Paradox and a New Role of Heat Shock Proteins and their Receptors as Anti-Inflammation Targets
Inflammation & Allergy - Drug Targets (Discontinued) Endothelial Dysfunction in Morbid Obesity
Current Pharmaceutical Design Increased Serum HMGB-1, ICAM-1 and Metalloproteinase-9 Levels in Buerger’s Patients
Current Vascular Pharmacology Possibility of Non-Immunosuppressive Immunophilin Ligands as Potential Therapeutic Agents for Parkinsons Disease
Current Pharmaceutical Design Nanotechnology Based Diagnostic and Therapeutic Strategies for Neuroscience with Special Emphasis on Ischemic Stroke
Current Medicinal Chemistry Discovery of Nesfatin-1 and Overview of Biological Actions and New Developments
Current Pharmaceutical Design Insulin-Like Growth Factor-1 and its Derivatives: Potential Pharmaceutical Application for Treating Neurological Conditions
Recent Patents on CNS Drug Discovery (Discontinued) Peptide5 Attenuates rtPA Related Brain Microvascular Endothelial Cells Reperfusion Injury via the Wnt/β-Catenin Signalling Pathway
Current Neurovascular Research Analysis of Edg-Like LPA Receptor-Ligand Interactions
Current Pharmaceutical Design Progress in Therapies for Myocardial Ischemia Reperfusion Injury
Current Drug Targets