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
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Occurrence, Functions and Biological Significance of Arginine-Rich Proteins
Current Protein & Peptide Science Gene Expression Studies to Investigate Disease Mechanisms in Rheumatoid Arthritis: Does Angiogenesis Play a Role?
Current Rheumatology Reviews Potential Therapeutic Effects of Oleuropein Aglycone in Alzheimer's Disease
Current Pharmaceutical Biotechnology Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection
Current Pharmaceutical Design Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry The Oxido-reductase Activity of the Apoptosis Inducing Factor: A Promising Pharmacological Tool?
Current Pharmaceutical Design Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies
Current Molecular Medicine The Cellular Effects of Carbon Monoxide in the Airway
Current Molecular Medicine Hydrogen Sulfide and its Modulation in Arterial Hypertension and Atherosclerosis
Cardiovascular & Hematological Agents in Medicinal Chemistry Gastric Cytoprotection Beyond Prostaglandins: Cellular and Molecular Mechanisms of Gastroprotective and Ulcer Healing Actions of Antacids
Current Pharmaceutical Design Editorial (Thematic Issues: Pharmacological Mechanisms and Interventions in Ischemia/ Reperfusion-Induced Injury)
Current Pharmaceutical Design The Potential for Substance P Antagonists as Anti-Cancer Agents in Brain Tumours
Recent Patents on CNS Drug Discovery (Discontinued) Cardiovascular Effects of Glucagon-Like Peptide 1
Mini-Reviews in Medicinal Chemistry Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction
Current Pharmaceutical Design Oxidative Stress and Mitochondrial Dysfunction in Type 2 Diabetes
Current Pharmaceutical Design The Potential Roles of Metallothionein as a Therapeutic Target for Cerebral Ischemia and Retinal Diseases
Current Pharmaceutical Biotechnology Discovery of Nesfatin-1 and Overview of Biological Actions and New Developments
Current Pharmaceutical Design Microvascular Obstruction After Primary Percutaneous Coronary Intervention: Pathogenesis, Diagnosis and Prognostic Significance
Current Vascular Pharmacology In Vivo Imaging of the Diseased Nervous System: An Update
Current Pharmaceutical Design The Coronary Collateral Circulation in Man
Current Cardiology Reviews