4-iodo-3-nitrobenzamide

• ChemBase ID: 68416
• Molecular Formular: C7H5IN2O3
• Molecular Mass: 292.03067
• Monoisotopic Mass: 291.93449003
• SMILES: C(=O)(c1cc(c(cc1)I)[N+](=O)[O-])N
• Canonical SMILES: [O-][N+](=O)c1cc(ccc1I)C(=O)N
• InChI: InChI=1S/C7H5IN2O3/c8-5-2-1-4(7(9)11)3-6(5)10(12)13/h1-3H,(H2,9,11)
• InChIKey: MDOJTZQKHMAPBK-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-iodo-3-nitrobenzamide
• IUPAC Traditional name: iniparib
• Synonyms: 4-Iodo-3-nitrobenzamide; Iniparib; NSC-746045; IND-71677; BSI-201; 4-Iodo-3-nitrobenzamide; BSI 201; Iniparib

Database IDs

• CAS Number: 160003-66-7
• MDL Number: MFCD11110639
• PubChem SID: 162034147
• PubChem CID: 9796068

CALCULATED PROPERTIES

• Acid pKa: 12.998284
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 1.6928145
• LogD (pH = 7.4): 1.6928158
• Log P: 1.6928148
• Molar Refractivity: 54.8194 cm^3
• Polarizability: 20.563086 Å^3
• Polar Surface Area: 86.23 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• TSCA Listed: false

Pharmacology Properties

• Target: PARP

Product Information

• Purity: 95+%
• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1087

Research Area

• Description: Cancer

Biological Activity

• Description: BSI-201 (Iniparib, SAR240550) is a PARP1 inhibitor.
• In Vitro: 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. ^[1] BSI-201 inhibits the growth of E-ras 20 cells, the effect of which can be augmented 4-fold when BOS is added. ^[2] 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. ^[3] 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. ^[4] 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. Although able to modestly sensitize cells to etoposide, BSI-201 fails to sensitize SKOV3 cells to topoisomerase I poisons, cisplatin, gemcitabine, or paclitaxel, or inhibit pADPr formation in situ at concentrations up to 100 μM. In contrast, BSI-201 is cytotoxic to a variety of cell lines at concentrations above 40 μM reflecting a mechanism independent of PARP. ^[5]

Combination Therapy

• Description: A Phase II study to assess the effect of BSI-201 in combination with gemcitabine/cisplatin in non-small cell lung cancer has been completed.

Protocol

• Protocol: Cell Assay ^[3]
• Cell Lines: MDA-MB-231, and MDA-MB-436
• Concentrations: Dissolved in DMSO, final concentrations ~10 μM
• Incubation Time: 5, and 9 days
• Methods: 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.

References

• References: [1] Mendeleyev J, et al. Biochem Pharmacol, 1995, 50(5), 705-714.
• References: [2] Bauer PI, et al. Biochem Pharmacol, 2002, 63(3), 455-462.
• References: [3] Liu X, et al. Clin Cancer Res, 2012, 18(2), 510-523.
• References: [4] Ma W, et al. Proc Natl Acad Sci U S A, 2012, 109(17), 6590-6595.
• References: [5] Patel AG, et al. Clin Cancer Res, 2012, 18(6), 1655-1662.

Toronto Research Chemicals - I657500

Iniparib is an irreversible PARP1 inhibitor. Studies show that potential therapeutic agent for the treatment of cancer, including triple-negative breast cancer.

REFERENCES

• Liu X, et al. Clin Cancer Res, 2012, 18(2), 510-523.
• Ma W, et al. Proc Natl Acad Sci U S A, 2012, 109(17), 6590-6595.
• Patel AG, et al. Clin Cancer Res, 2012, 18(6), 1655-1662.
• Mendeleyev J, et al. Biochem Pharmacol, 1995, 50(5), 705-714.
• Bauer PI, et al. Biochem Pharmacol, 2002, 63(3), 455-462.
• Liang, H. et al.: IDrugs, 13, 646 (2010)
• Liang, H. et al.: Curr. Breat Cancer Rep., 3, 44 (2010)
• O'Shaughnessy, J. et al.: N. Eng. J. Med., 364, 205 (2010)