Biological Activity

• DescriptionPARP1, also called as Poly(ADP-ribose) polymerase, is involved in the signaling of DNA damage. It can recognize and bind DNA single or double-strand breaks, thus possessing various cellular function, including regulation of apoptosis and chromosome stability, gene amplification and transcription, as well as cell division and differentiation. BSI-201 is a unique PARP1 inhibitor for its little inhibitory potency on PARP enzymatic activity. However, it can target the zinc finger domain and prevents PARP-1 activation by DNA breaks, as well as non-selectively modifies cysteine-containing proteins in tumor cells^[1][2]. The addition of DL-buthionine sulfoximine to BSI-201 produced a more significant effect on proliferation in MDA-MB-231 and MDA-MB-436 cells, whereas BSI-201 alone had little effect^[2]. A phase II trial of BSI-201 combined with gemcitabine and carboplatin for the treatment of TN breast cancer have been done^[3].
• MechanismBSI-201 targets the zinc finger domain and prevents PARP-1 activation by DNA breaks.^[1]

• Animal Study
  Dose	Hamster: 200 mg/kg[1] (i.p.)
  Administration	i.p.

• Clinical Study

• NCT Number	Condition or disease	Phase	Recruitment Status	Estimated Study Completion Date	Locations
  NCT01593228	Solid Tumors	Phase 3	Completed	-	-
  NCT01455532	Neoplasm Malignant	Phase 1	Completed	-	United States, Arizona ... more >> Investigational Site Number 840002 Scottsdale, Arizona, United States, 85258 United States, California Investigational Site Number 840004 Los Angeles, California, United States, 90048 United States, Georgia Investigational Site Number 840010 Augusta, Georgia, United States, 30912 United States, Missouri Investigational Site Number 840007 St Louis, Missouri, United States, 63110 United States, Ohio Investigational Site Number 840001 Cincinnati, Ohio, United States, 45267-0542 United States, Texas Investigational Site Number 840006 San Antonio, Texas, United States, 78229 Collapse <<
  NCT00813956	Triple Negative Breast Cancer	Phase 2	Completed	-	United States, California ... more >> Stanford Comprehensive Cancer Center Stanford, California, United States, 94305 United States, Pennsylvania PrECOG Philadelphia, Pennsylvania, United States, 19103 Collapse <<

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• References

• [1] Mendeleyev J, Kirsten E, et al. Potential chemotherapeutic activity of 4-iodo-3-nitrobenzamide. Metabolic reduction to the 3-nitroso derivative and induction of cell death in tumor cells in culture. Biochem Pharmacol. 1995 Aug 25;50(5):705-14.

  [2] Liu X, Shi Y, 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.

  [3] O'Shaughnessy J, Osborne C, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011 Jan 20;364(3):205-14.