product name Iniparib (BSI-201)
Description: Iniparib (also known as BSI-201) is a PARP1 inhibitor with demonstrated effectiveness in triple-negative breast cancer (TNBC). It has important antitumor activity and 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.
References: Biochem Pharmacol. 1995 Aug 25;50(5):705-14; Biochem Pharmacol. 2002 Feb 1;63(3):455-62; Clin Cancer Res. 2012 Jan 15;18(2):510-23.
292.03
Formula
C7H5IN2O3
CAS No.
160003-66-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 58 mg/mL (198.6 mM)
Water: <1 mg/mL
Ethanol: 28 mg/mL (95.9 mM)
Solubility (In vivo)
Synonyms
NSC-746045, IND-71677
other peoduct :
| In Vitro |
In vitro activity: BSI-201 is described as a prodrug of 4-iodo-3-nitrosobenzamide, an agent that covalently inhibits PARP1 by binding to its first zinc finger under cell-free conditions. Treatment of 120 μM BSI-201 plus buthionine sulfoximine (BSO) induces a 95% cell death among 855-2 cells, and displays a similar effect in other human cancer cells. BSI-201 inhibits the growth of E-ras 20 cells, the effect of which can be augmented 4-fold when BOS is added. Recently BSI-201 shows no ability to inhibit PARP enzymatic or cellular activity, but can non-selectively modify cysteine-containing proteins in tumor cells, suggesting the mechanism of action for BSI-201 is likely not via inhibition of PARP activity. BSI-201 (100 μM) inhibits ionizing radiation-induced single-strand breaks (SSBs) repair in human lymphoid cell lines based on large endogenous Epstein–Barr virus (EBV) circular episomes assay, resulting in 55% repair by 2 hours, which can be reversed surprisingly by knockdown of PARP1, indicating that the mechanism of inhibition does not involve trapping PARP at SSBs. BSI-201 is not able to selectively kill homologous recombination (HR)-deficient cells between BRCA2-deficient PEO1 and BRCA2-revertant PEO4, or ATM-deficient GM16666 and ATM-restored GM16667 fibroblasts. BSI-201 is cytotoxic to a variety of cell lines at concentrations above 40 μM reflecting a mechanism independent of PARP Kinase Assay: Cell Assay: Cells are exposed to various concentrations of BSI-201 for 5, and 9 days in the presence or absence of buthionine sulfoxamide (BSO). After treatment, cell proliferation is measured by CellTiter-Glo assay |
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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Biochem Pharmacol. 1995 Aug 25;50(5):705-14; Biochem Pharmacol. 2002 Feb 1;63(3):455-62; Clin Cancer Res. 2012 Jan 15;18(2):510-23. |
