MK-4827

SKU: orb1227085

Description

MK-4827 (Niraparib, MK4827) is 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 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.

Key Properties

• CAS Number: 1038915-60-4
• MW: 320.3883
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₀N₄O
• SMILES: C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
• Target: PARP
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• 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. Animal model: Female nude mice (Ncr Nu/Nu) with solitary tumor xenografts. 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.
• 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 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Niraparib | MK 4827 | MK4827

Quick Database Links

Gene Symbol

PARP