Small-molecule PARP modulators--current status and future therapeutic potential.
PARP-1 inhibitors have emerged as a promising therapeutic class of compounds, and numerous PARP inhibitors, including iniparib (BiPar Sciences Inc/sanofi-aventis), olaparib (AstraZeneca plc), veliparib (Abbott Laboratories), PF-1367338 (Pfizer Inc), MK-4827 (Merck & Co Inc) and CEP-9722 (Cephalon Inc), have advanced into clinical trials. Several additional inhibitors are expected to enter clinical trials within the next year. Early investigations with PARP-1 inhibitors involved non-oncological indications, but development has since progressed to focus primarily on oncology, for use both as single chemotherapeutic agents in specific patient populations (eg, BRCA-deficient) and as combination therapies with various chemotherapeutics. This review focuses on new developments in lead clinical PARP inhibitors, recent disclosures of new inhibitors and the potential use of PARP-1 inhibitors in new disease settings.
Penning
Thomas D
TD
Abbott Laboratories, Cancer Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA. thomas.penning@abbott.com
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D054852:Small Molecule Libraries