AG-014699

AG-014699 (PF-01367338, Rucaparib) is a PARP inhibitor with a Ki of 1.4 nM. AG-014699 is the phosphate salt of AG 014447 (CAS 283173-50-2) and has improved aqueous solubility. Poly (ADP-ribose) polymerases (PARPs) are activated by DNA single- and double-strand breaks and promote repair of DNA damage through the relaxation of chromatin and recruitment of other repair proteins. AG-014699 inactivates PARP activity in cells with homologous recombination DNA repair pathway mutations at LC50 values ranging from 1.3-5.5 μM. Radio-sensitization by AG-014699 is due to downstream inhibition of NF-κB activation, and independent of SSB repair inhibition. Although AG014699 can enhance response to some chemotherapeutic drugs via improved delivery, this does not apply to doxorubicin. PARP inhibitors may still be of use to counter doxorubicin toxicity.