AG014699

AG-014699 is a PARP inhibitor (Ki, 1.4 nmol/L) with outstanding in vivo chemosensitization potency, which is greater chemosensitization of temozolomide at a dose of 1 mg/kg than could be achieved with AG14361 at 10 mg/kg. Even a 10-fold lower dose of AG14447 (0.1 mg/kg) resulted in a 50% increase in the temozolomide-induced tumor growth delay. AG-014699, the phosphate salt of AG14447, which has improved aqueous solubility, has been selected for clinical trial. AG-014699 is a tricyclic indole poly(ADP-Ribose) polymerase (PARP) inhibitor with potential antineoplastic activity. PARP-1 inhibitor AG-014699 blocks base excision repair mediated by PARP 1 on single strand breaks and may be particularly efficacious in inducing apoptosis in breast cancer associated gene-1 and -2 (BRCA1/2) deficient tumor cells.