Iniparib

Iniparib (BSI-201) is an irreversible inhibitor of PARP1, used in the research of triple negative breast cancer.

4-iodo-3-nitrobenzamide is a carbonyl compound and an organohalogen compound.|Iniparib is a small molecule iodobenzamide with potential cytotoxic and antineoplastic activities. Although the mechanism of action is unknown, iniparib appears to be cytotoxic in cells with DNA alterations or DNA damage, like that found in tumor cells with mutations in the ataxia telangiectasia mutated (ATM) gene. ATM encodes a serine/threonine protein kinase and mutations of the gene are associated with ataxia telangiectasia and contribute to certain cancers such as T-cell acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia and B-cell non-Hodgkin lymphomas.

A solution of 3.7 g of methyl 4-iodo-3-nitrobenzoate and 30 mL of methanol was charged into a reaction flask, Stirring at 35 ° C, Through ammonia, TLCMonitoring the reaction process, the expansion agent volume ratio of ethyl acetate: petroleum ether = 1: 1. After completion of the reaction, The reaction was evaporated to dryness to give 3.3 g of crude product as a yellow solid. The crude product was recrystallized from 19.8 mL of ethanol and pumped to give a yellow crystal which was dried in vacuo to give 3.0 g of 4-iodo-3-nitrobenzamide, HPLC purity 99.75percent and yield 85.2percent.

Poly(ADP-ribose) polymerase (PARP) is a critical DNA repair enzyme involved in DNA single-strand break repair via the base excision repair pathway. PARP1 is activated by DNA damage. Inhibiting its activity has been linked to synthetic lethality and loss of either of the breast cancer susceptibility genes, BRCA1 and BRCA2. BSI-201 is an irreversible, noncompetitive inhibitor of PARP1 that disrupts binding between PARP1 and DNA by interacting with the DNA binding domain. It produces rapid apoptosis in various cancer cell lines with IC50 values ranging from 40-128 μM and is not toxic in Syrian hamsters at doses as high as 200 mg/kg. In phase II clinical studies, BSI-201, in combination with carboplatin and gemcitabine, has produced promising results in "triple-negative" breast cancers, increasing median overall survival from 7.7 months to 12.3 months.

Molecular Weight:292.03
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:291.93449
Monoisotopic Mass:291.93449
Topological Polar Surface Area:88.9
Heavy Atom Count:13
Complexity:228
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes