Niraparib tosylate CAS NO.1038915-73-9

MK–4827 tosylate is an excellent PARP1 and PARP2 inhibitor with IC50 of 3.8 and 2.1 nM, respectively. IC50 & Target: IC50: 3.8 nM (PARP1), 2.1 nM (PARP2).In Vitro: MK–4827 (Niraparib) inhibits PARP activity with EC50=4 nM and EC90=45 nM in a whole cell assay. MK–4827 inhibits proliferation of cancer cells with mutant BRCA–1 and BRCA–2 with CC50 in the 10-100 nM range. MK–4827 displays excellent PARP 1 and 2 inhibition with IC50=3.8 and 2.1 nM, respectively, and in a whole cell assay. To validate that MK–4827 (Niraparib) inhibits PARP in these cell lines, A549 and H1299 cells are treated with 1 μM MK–4827 for various times and measured PARP enzymatic activity using a chemiluminescent assay. The results show that MK–4827 inhibits PARP within 15 minutes of treatment reaching about 85% inhibition in the A549 cells at 1 h and about 55% inhibition at 1 h for the H1299 cells. In Vivo: MK–4827 is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA–1 deficient cancer. MK–4827 is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA–1 deficient cancer. MK–4827 is characterized by acceptable pharmacokinetics in rats with plasma clearance of 28 (mL/min)/kg, very high volume of distribution (Vdss=6.9 L/kg), long terminal half–life (t1/2=3.4 h), and excellent bioavailability, F=65%[1]. MK–4827 enhances radiation response of p53 mutant Calu–6 tumor in both cases, with the single daily dose of 50 mg/kg being more effective than 25 mg/kg given twice daily