Niraparib (MK-4827) tosylate hydrate 是高效的，具有生物口服利用度的PARP1和PARP2抑制剂，IC50分别为 3.8 nM 和 2.1 nM。Niraparib tosylate hydrate 抑制 DNA 损伤修复，诱导凋亡 (apoptosis) 并具有抗肿瘤活性。
| 生物活性 | Niraparib (MK-4827) tosylate hydrate is a highly potent and orally bioavailablePARP1andPARP2inhibitor withIC50s of 3.8 and 2.1 nM, respectively. Niraparib tosylate hydrate leads to inhibition of repair of DNA damage, activatesapoptosisand shows anti-tumor activity[1][2][3]. |
| IC50& Target | PARP-2 2.1 nM (IC50) | PARP-1 3.8 nM (IC50) | V-PARP 330 nM (IC50) | TANK-1 570 nM (IC50) | PARP-3 1300 nM (IC50) |
|
体外研究
(In Vitro) | Niraparib (MK-4827) tosylate hydrate inhibits PARP activity with EC50=4 nM and EC90=45 nM in a whole cell assay. Niraparib tosylate hydrate inhibits proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50in the 10-100 nM range. Niraparib tosylate hydrate displays excellent PARP 1 and 2 inhibition with IC50=3.8 and 2.1 nM, respectively, and in a whole cell assay[1].
Niraparib tosylate hydrate 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].
|
体内研究
(In Vivo) | Niraparib (MK-4827) tosylate hydrate is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer[1].
Niraparib (MK-4827) tosylate hydrate is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer[1].
Niraparib (MK-4827) tosylate hydrate 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].
Niraparib (MK-4827) tosylate hydrate 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].
| Animal Model: | Female nude mice (Ncr Nu/Nu) with solitary tumor xenografts[3] | | Dosage: | 25 mg/kg or 50 mg/kg | | Administration: | Gavage, 25 mg/kg twice a day with 6 h between doses or 50 mg/kg once daily for 21 consecutive days | | Result: | Enhanced radiation response. |
|
| Clinical Trial | |
| 分子量 | |
| Formula | |
| CAS 号 | |
| 中文名称 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
m.cnreagent.com