ABT-888 dihydrochloride, also known asVeliparib, is a potent and selective Poly (ADP-Ribose) Polymerase (PARP) Inhibitor. ABT-888 dihydrochloride enhances apoptosis and autophagy in response to treatments that cause DNA breaks, including radiation and DNA alkylation. ABT-888 dihydrochloride is an orally bioavailable inhibitor of PARP1 and PARP2 (Kis = 5.2 and 2.9 nM, respectively).
CAS Number: 912445-05-7
Molecular Weight: 317.21
ABT 888 dihydrochloride
Chemical Name: 2-[(2R)-2-methyl-2-pyrrolidinyl]-1H-benzimidazole-7-carboxamide, dihydrochloride
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Soluble in DMSO
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥360 days if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
ABT-888 dihydrochloride is inactive to SIRT2 (>5 μM). ABT-888 dihydrochloride inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 dihydrochloride can decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 dihydrochloride reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 dihydrochloride increases apoptosis and autophagy in H460 cells when combination with radiation. ABT-888 dihydrochloride inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 dihydrochloride (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 dihydrochloride shows effective radiosensitivity in oxic H1299 cells. ABT-888 dihydrochloride can attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1.
The oral bioavailability of ABT-888 dihydrochloride is 56%-92% in mice, SD rats, beagle dogs, and cynomolgus monkeys after oral administration. ABT-888 dihydrochloride (25 mg/kg, i.p.) can improve tumor growth delay in a NCI-H460 xenograft model. Combination with radiation, veliparib decreases the tumor vessel formation. ABT-888 dihydrochloride 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 can be maintained over time.
- Bhute VJ, Ma Y, Bao X, Palecek SP. The Poly (ADP-Ribose) Polymerase Inhibitor Veliparib and Radiation Cause Significant Cell Line Dependent Metabolic Changes in Breast Cancer Cells. Sci Rep. 2016 Nov 4;6:36061. doi: 10.1038/srep36061. PubMed PMID: 27811964; PubMed Central PMCID: PMC5095763.
- Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhász E, Urban L, Orlov S, Barlési F, Kio E, Keiholz U, Qin Q, Qian J, Nickner C, Dziubinski J, Xiong H, Ansell P, McKee MD, Giranda V, Gorbunova V. Randomized, Placebo-Controlled, Phase 2 Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer. Clin Cancer Res. 2016 Oct 10. pii: clincanres.3069.2016. [Epub ahead of print] PubMed PMID: 27803064.
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- Isakoff SJ, Puhalla S, Domchek SM, Friedlander M, Kaufman B, Robson M, Telli ML, Diéras V, Han HS, Garber JE, Johnson EF, Maag D, Qin Q, Giranda VL, Shepherd SP. A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. Future Oncol. 2016 Oct 14. [Epub ahead of print] PubMed PMID: 27739325.
- Chabot P, Hsia TC, Ryu JS, Gorbunova V, Belda-Iniesta C, Ball D, Kio E, Mehta M, Papp K, Qin Q, Qian J, Holen KD, Giranda V, Suh JH. Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study. J Neurooncol. 2016 Sep 21. [Epub ahead of print] PubMed PMID: 27655223.
- Subhash VV, Tan SH, Yeo MS, Yan FL, Peethala PC, Liem N, Krishnan V, Yong WP. ATM expression predicts Veliparib and Irinotecan sensitivity in gastric cancer by mediating P53 independent regulation of cell cycle and apoptosis. Mol Cancer Ther. 2016 Sep 16. pii: molcanther.1002.2015. [Epub ahead of print] PubMed PMID: 27638859.
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