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.