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PARP inhibitor
Potent inhibitor of PARP-1 and PARP-2 (potency ≤5nM in vitro). Does not inhibit other NAD-binding enzymes. Has minimal CYP450 inhibition and induction. Shows broad spectrum of chemo- and radiopotentiation. Is toxic to both oxic and hypoxic cells. Enantiomeric purity ≥97% suitable for in vivo studies. Does not show inherent cytotoxicity and shows no single agent activity in tumor models. Has excellent bioavailability and good blood-brain permeation. Increases tumor growth delay resulting from radiation and DNA-damaging agents.
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Product Details
| Alternative Name |
2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide . dihydrochloride |
|---|---|
| Appearance |
Colorless to white crystalline solid. |
| CAS |
912445-05-7 |
| Couple Target |
PARP |
| Couple Type |
Inhibitor |
| Formula |
C13H16N4O . 2HCl |
| Identity |
Identity determined by 1H-NMR. |
| MW |
244.3 . 73.0 |
| Purity |
≥98% (HPLC) |
| Solubility |
Soluble in water or DMSO. |
Handling & Storage
| Use/Stability |
As indicated on product label or CoA when stored as recommended. |
|---|---|
| Long Term Storage |
-20°C |
| Shipping |
Ambient Temperature |
| Regulatory Status |
RUO – Research Use Only |
|---|
- Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma: Dharanipragada, P., Zhang, X., et al.; Cancer Discov. 13, 880 (2023), Abstract
- PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality: Yakovlev, V. A., Sullivan, S. A., et al.; Front. Oncol. 13, 1124147 (2023), Abstract
- The interplay of TARG1 and PARG protects against genomic instability: Groslambert, J., Prokhorova, E., et al.; Cell Rep. 42, 113113 (2023), Abstract
- Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease: Prokhorova, E., Agnew, T., et al.; Mol. Cell 81, 2640 (2021), Abstract
- Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1: C. Morris, et al.; Oncotarget 12, 649 (2021), Abstract — Full Text
- Tissue-Specific Regulation of the Wnt/β-Catenin Pathway by PAGE4 Inhibition of Tankyrase: Koirala, S., Klein, J., et al.; Cell Rep. 32, 107922 (2020), Abstract
- Analysis of PARP inhibitor toxicity by multidimensional fluorescence microscopy reveals mechanisms of sensitivity and resistance: J. Michelena, et al.; Nat. Commun. 9, 2678 (2018), Abstract — Full Text
- p53 coordinates base excision repair to prevent genomic instability: M. Poletto, et al.; Nucleic Acids Res. 44, 3165 (2016), Application(s): Cell culture, Abstract — Full Text
- Disrupted ADP-ribose metabolism with nuclear Poly (ADP-ribose) accumulation leads to different cell death pathways in presence of hydrogen peroxide in procyclic Trypanosoma brucei: M. Schlesinger, et al.; Parasit. Vectors 9, 173 (2016), Application(s): Potency of inhibitors, Abstract — Full Text
- ABT-888 and Quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via Adenomatous polyposis coli: S. Siddharth, et al.; DNA Repair (Amst.) 45, 44 (2016), Application(s): Cell culture, Abstract
- Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways: R. Ghosh, et al.; DNA Repair (Amst.) 45, 56 (2016), Application(s): Genomic instability in metaphase spreads of wt and H2afx-/- activated B cells, Abstract
- p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity: C. Adriaens, et al.; Nat. Med. 22, 861 (2016), Application(s): Long-term growth assays, Abstract — Full Text
- Increased in vitro and in vivo sensitivity of BRCA2-associated pancreatic cancer to the poly(ADP-ribose) polymerase-1/2 inhibitor BMN 673: A.Z. Andrei, et al.; Cancer Lett. 364, 8 (2015), Application(s): Cell Culture, Abstract
- Synergistic enhancement of 5-fluorouracil cytotoxicity by deoxyuridine analogs in cancer cells: Y. Matsumoto, et al.; Oncoscience 2, 272 (2015), Abstract
- DNA double strand break repair defect and sensitivity to poly ADP-ribose polymerase (PARP) inhibition in human papillomavirus 16-positive head and neck squamous cell carcinoma: Weaver, A. N., Cooper, T. S., et al.; Oncotarget 6, 26995 (2015), Abstract
- Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts on metastasis free survival in breast cancer patients: Chiker, S., Pennaneach, V., et al.; Cell Cycle 14, 3066 (2015), Abstract
- Role for DNA damage signaling in pulmonary arterial hypertension: J. Meloche, et al.; Circulation 129, 786 (2014), Abstract
- 53BP1 mediates the fusion of mammalian telomeres rendered dysfunctional by DNA-PKcs loss or inhibition: I. Rybanska-Spaeder, et al.; PLoS One 9, e10873 (2014), Abstract — Full Text
- Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma: L. Barazzuol, et al.; Radiat. Oncol. 8, 65 (2013), Abstract — Full Text
- The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment: L.J. Monteiro, et al.; Oncogene 32, 4634 (2013), Abstract
- ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status: C.J. Huntoon, et al.; Cancer Res. 73, 3683 (2013), Abstract
- Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells: W. Wu, et al.; BBRC 442, 127 (2013), Abstract
- Inhibition of poly(ADP-ribose) polymerase-1 or poly(ADP-ribose) glycohydrolase individually, but not in combination, leads to improved chemotherapeutic efficacy in HeLa cells: X. Feng, et al.; Int. J. Onc. 42, 749 (2013), Abstract — Full Text
- The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation: Bolin, C., Boudra, M. T., et al.; Cell. Mol. Life Sci. 69, 951 (2012), Abstract
- Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells: A.G. Patel, et al.; PNAS 108, 3406 (2011), Abstract
- Disposition and Drug-Drug Interaction Potential of Veliparib (ABT-888), a Novel and Potent Inhibitor of Poly(ADP-ribose) Polymerase: X. Li, et al.; Drug Metab. Dispos. 39, 1161 (2011), Abstract
- Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130: D.C. Hegan, et al.; PNAS 107, 2201 (2010), Abstract — Full Text
- PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors: B. McEllin, et al.; Cancer Res. 70, 5457 (2010), Abstract
- Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates: J.A. Muscal, et al.; Cancer Chemother. Pharmacol. 65, 419 (2010), Abstract
- Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway: Hajkova, P., Jeffries, S. J., et al.; Science 329, 78 (2010), Abstract
- Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer: T.D. Penning, et al.; J. Med. Chem. 52, 514 (2009), Abstract
- A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia: S.K. Liu, et al.; Radiother. Oncol. 88, 258 (2008), Abstract
- ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models: C.K. Donawho, et al.; Clin. Cancer Res. 13, 2728 (2007), Abstract
- Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models: J.M. Albert, et al.; Clin. Cancer Res. 13, 3033 (2007), Abstract
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