N-5665 Niraparib, Free Base, >99%

Synonyms : [MK-4827]

Related Terms : [Zejula]

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  • 1 g
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  • M.W. 320.39
  • C19H20N4O
  • [1038915-60-4]

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  • Niraparib, also known as MK-4827, is a poly(ADP-ribose)polymerase (PARP) inhibitor.  Niraparib displayed excellent PARP 1 and 2 inhibition with IC50 values of 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with an IC50 of 4 nM, and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2, with IC50 values of 10-100 nM.  Niraparib was well tolerated in vivo and showed antitumor activity as a single agent in a xenograft model of BRCA-1 deficient cancer.  Jones P., et al. "Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors." J. Med. Chem. 52: 7170-7185 (2009).
  • Niraparib enhanced radiation-induced cytotoxicity in neuroblastoma cells.  In vivo treatment with niraparib and radiation prolonged survival of mice in a murine xenograft model of metastatic neuroblastoma when compared to single modalities.  Mueller S., et al. "Poly (ADP-Ribose) polymerase inhibitor MK-4827 together with radiation as a novel therapy for metastatic neuroblastoma." Anticancer Res. 33: 755-762 (2013).
  • A phase 1 clinical trial demonstrated niraparib inhibited PARP more than 50% at doses greater than 80 mg/day and had antitumour activity at doses beyond 60 mg/day.  Antitumour activity of niraparib was reported in BRCA1 or BRCA2 mutation carriers with ovarian cancer, breast cancer, and in patients with sporadic high-grade serous ovarian cancer, non-small-cell lung cancer, and prostate cancer.  Sandhu S.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 Oncol. 14: 882-892 (2013).
  • Related  CAS numbers: 1038915-64-8 for the hydrochloride salt; 1038915-73-9 for the methanesulfonate salt; 1171196-88-5 for the sulfate salt.
  • Niraparib (as the Tosylate monohydrate) is the active ingredient in the drug sold under the trade name Zejula®. This drug has been approved in at least one country for use in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. NOTE: THE NIRAPARIB SOLD BY THE LC LABORATORIES IS NOT ZEJULA®, AND IS NOT FOR HUMAN USE.
  • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
  • This  product is offered for R&D use in accordance with (i) 35 USC  271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in  Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in  Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977  in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law  exemptions of Canadian patent law; (vi) Section 68B of the Patents Act  of 1953 in New Zealand together with the amendment of same by the  Statutes Amendment Bill of 2002; (vii) such related legislation and/or  case law as may be or become applicable in the aforementioned countries;  and (viii) such similar laws and rules as may apply in various other  countries.
  • Not available in some countries; not available to some institutions; not available for some uses.
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