Niraparib tosylate (MK-4827 tosylate) is a highly potent and orally bioavailablePARP1andPARP2inhibitor with anIC₅₀of 3.8 and 2.1 nM, respectively. Niraparib tosylate leads to inhibition of repair of DNA damage, activatesapoptosisand shows anti-tumor activity^[1][2][3].

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 CC₅₀in 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^[1]. 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^[2].

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 (Vd_ss=6.9 L/kg), long terminal half-life (t_1/2=3.4 h), and excellent bioavailability, F=65%^[1]. 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^[3].

492.59

Solid

C₂₆H₂₈N₄O₄S

1038915-73-9

尼拉帕尼对苯甲磺酸盐

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : 100 mg/mL(203.01 mM;ultrasonic and warming and heat to 60℃)

H₂O : 1 mg/mL(2.03 mM;heat to 50℃)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 5% DMSO    40%PEG300   5%Tween-80   50% saline

  Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution
• 2.

  请依序添加每种溶剂： 5% DMSO    95% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution
• 3.

  请依序添加每种溶剂： 1% DMSO    99% saline

  Solubility: ≥ 0.5 mg/mL (1.02 mM); Clear solution