Veliparib dihydrochloride is a potent inhibitor of PARP-1 and PARP-2 with K (i) s of 5.2 and 2.9 nmol/L, respectively [1].
PARP is short of poly ADP ribose polymerase and is reported as an overexpressed enzyme in a variety of cancers. Since it has been revealed that several forms of cancer more independent on PARP compared with regular cells, which making PARP as an attractive target for cancer therapy. Many studies have shown that PARP inhibitors act as radio- and chemotherapy- sensitizers in preclinical studies using both in vitro and in vivo models [2] [3].
Veliparib dihydrochloride is a selective inhibitor of PARP. When tested with colon cancer cell lines HCT-116 and HT-29, using veliparib dihydrochloride as an adjuvant and combing with SN38 or Oxall resulted in increasing G2/M cell cycle arrest and increased levels of DNA damage via inhibiting PARP-1 and PARP-2 [4].
In mouse model with B16F10 murine melanoma cells injected subcutaneously, oral administration of veliparib dihydrochloride with temozolomide increased the efficacy at the concentration of 3.1 mg/kg/d~25 mg/kg/d and markedly slowed tumor progression. And similar results were achieved when tested with MX-1 breast xenograft model (BRCA1 deletion and BRCA2 mutation) or HCT-116 colon carcinoma model [1].
References:
[1].    Donawho, C.K., et al., ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res, 2007. 13(9): p. 2728-37.
[2].    Benafif, S. and M. Hall, An update on PARP inhibitors for the treatment of cancer. Onco Targets Ther, 2015. 8: p. 519-28.
[3].    Guillot, C., et al., PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models. BMC Cancer, 2014. 14: p. 603.
[4].    Davidson, D., et al., The PARP inhibitor ABT-888 synergizes irinotecan treatment of colon cancer cell lines. Invest New Drugs, 2013. 31(2): p. 461-8.