Veliparib
CAS#: 912444-00-9
Description: Veliparib, also known as ABT-888, is a poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor with chemosensitizing and antitumor activities. With no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents.
Synonym: ABT888; ABT-888; ABT 888; Veliparib
IUPAC/Chemical Name: (R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide
THEORETICAL ANALYSIS
Name: Veliparib
CAS#: 912444-00-9
Chemical Formula: C13H16N4O
Exact Mass: 244.13241
Molecular Weight: 244.29
Elemental Analysis: C, 63.91; H, 6.60; N, 22.93; O, 6.55
TECHNICAL DATA
ADDITIONAL INFORMATION
PARP nuclear enzymes are activated by DNA single or double strand breaks, resulting in the poly(ADP-ribosyl)ation of other nuclear DNA binding proteins involved in DNA repair; poly(ADP-ribosyl)ation contributes to efficient DNA repair and to survival of proliferating cells exposed to mild genotoxic stresses as induced by as oxidants, alkylating agents or ionizing radiation..
REFERENCES
1: Ji J, Kinders RJ, Zhang Y, Rubinstein L, Kummar S, Parchment RE, Tomaszewski JE, Doroshow JH. Modeling pharmacodynamic response to the poly(ADP-Ribose) polymerase inhibitor ABT-888 in human peripheral blood mononuclear cells. PLoS One. 2011;6(10):e26152. Epub 2011 Oct 10. PubMed PMID: 22028822; PubMed Central PMCID: PMC3189959.
2: Kummar S, Chen A, Ji J, Zhang Y, Reid JM, Ames M, Jia L, Weil M, Speranza G, Murgo AJ, Kinders R, Wang L, Parchment RE, Carter J, Stotler H, Rubinstein L, Hollingshead M, Melillo G, Pommier Y, Bonner W, Tomaszewski JE, Doroshow JH. Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas. Cancer Res. 2011 Sep 1;71(17):5626-34. Epub 2011 Jul 27. PubMed PMID: 21795476; PubMed Central PMCID: PMC3166628.
3: Nowsheen S, Bonner JA, Yang ES. The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy. Radiother Oncol. 2011 Jun;99(3):331-8. Epub 2011 Jun 28. PubMed PMID: 21719137; PubMed Central PMCID: PMC3157293.
4: Li X, Delzer J, Voorman R, de Morais SM, Lao Y. Disposition and drug-drug interaction potential of veliparib (ABT-888), a novel and potent inhibitor of poly(ADP-ribose) polymerase. Drug Metab Dispos. 2011 Jul;39(7):1161-9. Epub 2011 Mar 24. PubMed PMID: 21436403.
5: Karlberg T, Hammarström M, Schütz P, Svensson L, Schüler H. Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888. Biochemistry. 2010 Feb 16;49(6):1056-8. PubMed PMID: 20092359.
6: Reinhardt S, Zhao M, Mnatsakanyan A, Xu L, Ricklis RM, Chen A, Karp JE, Rudek MA. A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS. J Pharm Biomed Anal. 2010 May 1;52(1):122-8. Epub 2009 Dec 29. PubMed PMID: 20071126; PubMed Central PMCID: PMC2822340.
7: Phillips LR, Hill KD, Majerova E. Liquid Chromatographic Determination of NSC 737664 (ABT-888: an Inhibitor of Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical Trial. J Liq Chromatogr Relat Technol. 2009 Jan;32(2):261-272. PubMed PMID: 20046211; PubMed Central PMCID: PMC2615403.
8: Wiegand R, Wu J, Sha X, LoRusso P, Li J. Simultaneous determination of ABT-888, a poly (ADP-ribose) polymerase inhibitor, and its metabolite in human plasma by liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Feb 1;878(3-4):333-9. Epub 2009 Nov 27. PubMed PMID: 20005184.
9: Palma JP, Wang YC, Rodriguez LE, Montgomery D, Ellis PA, Bukofzer G, Niquette A, Liu X, Shi Y, Lasko L, Zhu GD, Penning TD, Giranda VL, Rosenberg SH, Frost DJ, Donawho CK. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin Cancer Res. 2009 Dec 1;15(23):7277-90. Epub 2009 Nov 24. PubMed PMID: 19934293.
10: Liu X, Han EK, Anderson M, Shi Y, Semizarov D, Wang G, McGonigal T, Roberts L, Lasko L, Palma J, Zhu GD, Penning T, Rosenberg S, Giranda VL, Luo Y, Leverson J, Johnson EF, Shoemaker AR. Acquired resistance to combination treatment with temozolomide and ABT-888 is mediated by both base excision repair and homologous recombination DNA repair pathways. Mol Cancer Res. 2009 Oct;7(10):1686-92. Epub 2009 Oct 13. PubMed PMID: 19825992.
