MK-4827 tosylate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种高效 PARP 抑制剂，对 PARP1/PARP2 的 IC50 为 3.8 nM/2.1 nM。

A highly potent PARP inhibitor with IC50 of 3.8 nM/2.1 nM for PARP1/PARP2; inhibits PARP activity with EC50=4 nM in a whole cell assay, and inhibits proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10?100 nM range; well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.Ovarian Cancer Approved(In Vitro):Niraparib (MK-4827) 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 Niraparib (MK-4827) inhibits PARP in these cell lines, A549 and H1299 cells are treated with 1 μM Niraparib (MK-4827) for various times and measured PARP enzymatic activity using a chemiluminescent assay. The results show that Niraparib (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):Niraparib (MK-4827) is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (MK-4827) is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (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%. Niraparib (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.

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Niraparib tosylate | MK 4827 tosylate | MK4827 tosylate

Cell Cycle/DNA Damage

PARP

PARP1|PARP2

Cancer

Ovarian Cancer

1038915-73-9

492.5899

C26H28N4O4S

>98% (HPLC)

DMSO: ≥ 490 mg/mL

CC1=CC=C(C=C1)S(=O)(=O)O.C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N

2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]-, 4-methylbenzenesulfonate (1:1)

(-20℃)

With Ice Pack

≥ 2 years