Niraparib HCl (MK-4827)

Description: Niraparib HCl (formerly known as MK-4827) is a potent, orally bioavailable and selective inhibitor of PARP1/2 with IC50 of 3.8 nM and 2.1nM for PARP 1 and 2 respectively. Niraparib is approved by the US FDA on 27 March 2017 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. Niraparib demonstrated high activity in cancer cells with mutant BRCA-1 and BRCA-2 with IC50 in the 10?100 nM range. It is > 330-fold selective against PARP3, V-PARP and Tank1. 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. MK-4827 strongly enhanced the effect of radiation on a variety of human tumor xenografts, both p53 wild type and p53 mutant.

References: Invest New Drugs. 2012 Dec; 30(6):2113-20; J Med Chem. 2009 Nov 26; 52(22):7170-85.

Related CAS #: 1038915-73-9 (tosylate); 1038915-60-4 (free base); 1613220-15-7 (tosylate hydrate); 1476777-06-6 (Niraparib metabolite M1); 1038915-58-0 (Niraparib R-enantiomer)