1038915-60-4 Usage
Uses
Niraparib is a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors.
Description
(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.
Pharmacology
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.
in vitro
mk-4827displayed excellent parp 1 and 2 inhibition with ic50 of 3.8 and 2.1 nm, respectively. in a whole cell assay, mk-4827 inhibited parp activity with ec50 of 4 nm. mk-4827 also inhibited proliferation of cancer cells with mutant brca-1 and brca-2 with cc50 in the 10-100 nm range[1].
in vivo
in a variety of human tumor xenografts of differing p53 status,mk-4827 showed high potential to improve the efficacy of radiotherapy,such as calu-6 (p53 null), a549 (p53 wild-type [wt]) and h-460 (p53 wt) lung cancers and triple negative mda-mb-231 human breast carcinoma [3].
References
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1038915-60-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,3,8,9,1 and 5 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1038915-60:
(9*1)+(8*0)+(7*3)+(6*8)+(5*9)+(4*1)+(3*5)+(2*6)+(1*0)=154
154 % 10 = 4
So 1038915-60-4 is a valid CAS Registry Number.
1038915-60-4Relevant articles and documents
Niraparib preparation method
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, (2021/11/14)
The invention provides a niraparib preparation method, which comprises: carrying out photocatalysis on a compound 1 and bromobenzene under a Pd catalyst to obtain a niraparib key intermediate; carrying out chiral resolution on the niraparib key intermediate, and coupling the niraparib key intermediate with NBoc-1H-indazole-7-carboxamide under the catalysis of copper bromide to obtain protected niraparib; and removing the protective color of the protected niraparib under the action of methanesulfonic acid, and obtaining the target product niraparib under tetrahydrofuran pulping. The preparation method of niraparib is simple in synthesis process route, high in preparation efficiency, small in damage to human bodies and the environment and low in synthesis cost.
NIRAPARIB SALTS
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Paragraph 000404-000406, (2020/05/15)
Novel salts of niraparib are provided. Also provided are pharmaceutical compositions comprising those salts, as well as methods and uses pertaining to the same.
COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATMENT OF DISEASES INVOLVING ACIDIC OR HYPOXIC DISEASED TISSUES
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Page/Page column 136; 137, (2019/07/20)
Compounds for treatment of diseases having acidic or hypoxic diseased tissues and pharmaceutical compositions comprising the compounds, as well as methods for making and using the compounds and compositions.