PARP inhibitors: polypharmacology versus selective inhibition.

Abstract

Inhibition of ADP-ribosyltransferases with diphtheria toxin homology (ARTD), widely known as the poly(ADP-ribose) polymerase (PARP) family, is a strategy under development for treatment of various conditions, including cancers and ischemia. Here, we give a brief summary of ARTD enzyme functions and the implications for their potential as therapeutic targets. We present an overview of the PARP inhibitors that have been used in clinical trials. Finally, we summarize recent insights from structural biology, and discuss the molecular aspects of PARP inhibitors in terms of broad-range versus selective inhibition of ARTD family enzymes.

• Authors: Torun Ekblad, Emidio Camaioni, Herwig Schüler, Antonio Macchiarulo
• Journal: The FEBS journal (FEBS J) Vol. 280 Issue 15 Pg. 3563-75 (Aug 2013) ISSN: 1742-4658 [Electronic] England
• PMID: 23601167 (Publication Type: Journal Article, Review)
• Copyright: © 2013 The Authors Journal compilation © 2013 FEBS.

Chemical References

• Antineoplastic Agents
• Indoles
• Poly(ADP-ribose) Polymerase Inhibitors
• Dacarbazine
• rucaparib
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Temozolomide

Topics

• Amino Acid Motifs
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Catalytic Domain
• Clinical Trials as Topic
• Dacarbazine (analogs & derivatives, pharmacology)
• Humans
• Indoles (chemistry, pharmacology)
• Models, Molecular
• Neoplasms (drug therapy, enzymology)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerase Inhibitors
• Temozolomide