A PARP1 inhibitor
Iniparib, previously named BSI-201, is an intravenously administered PARP1 inhibitor, which either alone or in combination with chemotherapy, has important antitumor activity in studies in vitro and in vivo. It is active against a broad range of cancer cells in culture, including drug resistant cell lines. Iniparib has been reported to be a prodrug whose C-nitroso metabolite, 4-iodo-3-nitrosobenzamide, selectively kills tumor cells by oxidizing the zinc finger of PARP-1 resulting in ejection of zinc and inhibition of PARP activity.
Reference
[1].Liang H, Tan AR. Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including triple-negative breast cancer. IDrugs. 2010 Sep;13(9):646-56.
[2].Xuesong Liu, Yan Shi, David X. Maag, Joann P. Palma, Melanie J. Patterson, Paul A. Ellis, Bruce W. Surber, Damien B. Ready, Niru B. Soni, Uri S. Ladror, Allison J. Xu, Ramesh Iyer, John E. Harlan, Larry R. Solomon, Cherrie K. Donawho, Thomas D. Penning, Eric F. Johnson, Alexander R. Shoemaker. Iniparib Nonselectively Modifies Cysteine-Containing Proteins in Tumor Cells and Is Not a Bona Fide PARP Inhibitor. Clinical Cancer Research. January 15, 2012 18; 510.
[3].S. Kopetz, M. M. Mita, I. Mok, K. K. Sankhala, J. Moseley, B. M. Sherman, C. R. Bradley and A. W. Tolcher. First in human phase I study of BSI-201, a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in subjects with advanced solid tumors. Journal of Clinical Oncology. (Meeting Abstracts) May 2008 vol. 26 no. 15_suppl 3577
Cell experiment: | For nine day cell proliferation assay, MDA-MB-436 and MDA-MB-231 cells are plated at 2000 and 500 cells/well respectively in a 96-well plate and treated with veliparib, cmpd-A, cmpd-C, Iniparib or Iniparib-met at 0, 0.0001, 0.01,0.1, 1 or 10 μM for nine days. For five day cell proliferation assay, MDAMB-231 and MDA-MB-436 cells are plated at 1000 and 4000 cells/well respectively in a 96-well plate and treated with Iniparib or Iniparib-met at 0. 0.1, 0.3, 1, 3 or 10 μM in the presence of 0, 1.8, 3.75, or 7.5 μM BSO for 5 days. DLD1+/+ and DLD1-/- cells are plated at 1000 cells/well in a 96-well plate and treated with TMZ at 0, 0.003, 0.01, 0.03, 0.1, 0.3 or 1 mM in the presence of 0, 0.005, 0.05, 0.5, or 5 μM veliparib, or Iniparib for five days. After treatment, cell titer glow is carried out[1]. |
参考文献: [1]. Liu X, et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor. Clin Cancer Res. 2012 Jan 15;18(2):510-23. | |
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