product name Veliparib (ABT-888)
Description: Veliparib (ABT-888) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. ABT-888 has demonstrated excellent in vivo efficacy in a broad spectrum of preclinical tumor models in combination with a variety of cytotoxic agents. ABT-888 is also active on microsatellite instability (MSI) cell lines harboring mutations in both MRE11 and RAD50 genes compared to microsatellite stable (MSS) cell lines (wild-type for both genes).
References: Clin Cancer Res. 2007 May 1;13(9):2728-37; Clin Cancer Res. 2007 May 15;13(10):3033-42; Clin Cancer Res. 2008 Nov 1; 14(21): 6877–6885.
244.29
Formula
C13H16N4O
CAS No.
912444-00-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 17 mg/mL (69.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose+0.2% Tween 80: 5 mg/mL
Synonyms
NSC 737664
other peoduct :
| In Vitro |
In vitro activity: ABT-888 is inactive to SIRT2 (>5 μM). ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 increases apoptosis and autophagy in H460 cells when combination with radiation. ABT-888 also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 shows effective radiosensitivity in oxic H1299 cells. Furthermore, ABT-888 could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1. Kinase Assay: Cell Assay: In HCT-116 and HT-29 cell lines, the ability of ABT-888 to synergize the effect of the anti-cancer agents, SN38 or oxaliplatin, was determined using the SRB assay. PARP activity was significantly reduced in samples treated with SN38 in combination with ABT-888 (>4 fold at 24 h). |
|---|---|
| In Vivo | The oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. ABT-888 (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, ABT-888 decreases the tumor vessel formation. ABT-888 reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models and the suppression could be maintained over time. |
| Animal model | Female nude athymic mice |
| Formulation & Dosage | Dissolved in solution containing 0.9% NaCl adjusted to pH 4.0; 55mg/kg; Oral administration |
| References | Clin Cancer Res. 2007 May 1;13(9):2728-37; Clin Cancer Res. 2007 May 15;13(10):3033-42; Clin Cancer Res. 2008 Nov 1; 14(21): 6877–6885. |
