Нирапариб

Описание

(S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide is also known as MK-4827(Niraparib) tosylate is a selective inhibitor of PARP1/PARP2 (The poly(ADP-ribose) polymerase) with great activity in cancer cells with mutant BRCA-1 and BRCA-2. It has been recently approved by FDA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death.

Использование

Niraparib is a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors.

Фармаколо?гия

The synthesis and initial pharmacology of niraparib have been published. Niraparib has affinity for PARP 1 and 2 inhibition (IC50 = 3.8 and 2.1 nM, respectively) and inhibits the proliferation of cancer cells with mutant BRCA1 and BRCA2 with IC50 values in the 10–100 nM range in vitro. Niraparib demonstrated efficacy as a single agent in a xenograft model of BRCA1-deficient cancer. Niraparib has also been reported to act as a preclinical radiosensitiser and has entered into clinical oncology trials.

использованная литература

https://newdrugapprovals.org/2016/12/22/niraparib-mk-4827/
https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm548487.htm
https://www.drugbank.ca/drugs/DB11793
Sandhu, Shahneen K, et al. "The poly (ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA, mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial." Lancet Oncology14.9 (2013):882.
Jones, P, et al. "Niraparib: A Poly (ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. " Journal of Medicinal Chemistry 58.8(2015):3302-14.