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| 25mg |
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Purity: ≥98%
Niraparib (formerly known as MK4827; MK-4827; Zejula) is a potent, orally bioavailable and selective inhibitor of PARP1/2 with anticancer activity. It inhibits PARP1/2, with IC50 values for PARP 1 and 2 of 3.8 nM and 2.1 nM, respectively. On March 27, 2017, the US FDA approved niraparib for the maintenance of patients who are responding either completely or partially to platinum-based chemotherapy and have recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. In cancer cells exhibiting mutated BRCA-1 and BRCA-2, niraparib exhibited significant efficacy, with an IC50 within the 10−100 nM range. It has a >330-fold selectivity against Tank1, V-PARP, and PARP3. MK-4827 inhibited PARP activity in a whole cell assay, with an EC50 of 4 nM. Moreover, MK-4827 slowed the growth of cancer cells harboring mutated BRCA-1 and BRCA-2, with CC50 values between 10 and 100 nM. On a range of human tumor xenografts, including p53 wild type and p53 mutant tumors, MK-4827 significantly increased the impact of radiation.
| Targets |
PARP-2 ( IC50 = 2.1 nM ); PARP-1 ( IC50 = 3.8 nM ); V-PARP ( IC50 = 330 nM ); TANK-1 ( IC50 = 570 nM ); PARP-3 ( IC50 = 1300 nM )
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| Enzyme Assay |
In a whole cell assay, MK-4827 inhibits PARP activity with EC(50) = 4 nM and prevents the growth of cancer cells expressing mutant BRCA-1 and BRCA-2 with CC(50) in the 10-100 nM range. It also exhibits excellent inhibition of PARP 1 and 2 with IC(50) = 3.8 and 2.1 nM, respectively.
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| Cell Assay |
In 96-well black viewplates, proliferation assays were carried out. 300 cells/well (250 cells/well for BRCA-1 wt) in culture medium, 190 μL/well (DMEM containing 10% FCS, 0.1 mg/mL penicillin-streptomycin, and 2 mM L-glutamine), were plated, and the cells were incubated for 4 hours at 37°C in an atmosphere of 5% CO2. Next, in 0.5% DMSO, inhibitors were added in serial dilutions of 10 μL/well until the final compound concentration was as desired. The viability of the cells was then evaluated after they had been incubated for 7 days at 37°C in 5% CO2. In brief, after adding 100 μL/well of prediluted 1:10 CellTiter-Blue solution to the medium, the cells were incubated for 45 minutes at 37°C with 5% CO2 and then for an additional 15 minutes at room temperature in the dark. By reading the plate at a fluorimeter, excitation at 550 nm, and emission at 590 nm, the number of living cells was ascertained. The percentage growth of the cells in comparison to the vehicle-treated cells was used to express the cell growth. It was established what concentration (CC50) was needed to stop cell growth by 50%.
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| References |
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| Molecular Formula |
C19H20N4O
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| Molecular Weight |
320.39
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| Exact Mass |
320.4
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| Elemental Analysis |
C, 71.23; H, 6.29; N, 17.49; O, 4.99
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| CAS # |
1038915-60-4
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| Related CAS # |
1038915-60-4; 1038915-73-9; 1038915-64-8 (HCl); 1613220-15-7 (tosylate hydrate); 1476777-06-6 (Niraparib metabolite M1); 1038915-58-0 (Niraparib R-enantiomer)
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| Appearance |
Light yellow solid powder
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| SMILES |
C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
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| InChi Key |
PCHKPVIQAHNQLW-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C19H20N4O/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24)/t14-/m1/s1
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| Chemical Name |
2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide
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| Synonyms |
MK-4827; MK 4827; Niraparib free base; Zejula; MK4827;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1212 mL | 15.6060 mL | 31.2120 mL | |
| 5 mM | 0.6242 mL | 3.1212 mL | 6.2424 mL | |
| 10 mM | 0.3121 mL | 1.5606 mL | 3.1212 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04313504 | Active Recruiting |
Drug: Niraparib Drug: Dostarlimab |
Head and Neck Cancer | Trisha Wise-Draper | November 4, 2020 | Phase 2 |
| NCT03601923 | Active Recruiting |
Drug: Niraparib | Pancreatic Cancer | Pancreatic Cancer | August 22, 2018 | Phase 2 |
| NCT05169437 | Active Recruiting |
Drug: Niraparib | Solid Tumor Breast Tumor |
Tempus Labs | March 15, 2022 | Phase 2 |
| NCT05515575 | Active Recruiting |
Drug: Niraparib | Sarcoma,Soft Tissue Sarcoma Uterus |
Memorial Sloan Kettering Cancer Center |
August 23, 2022 | Phase 2 |
| NCT03840967 | Active Recruiting |
Drug: Niraparib | Esophageal Cancer Gastric Cancer |
Shadia Jalal, MD | July 9, 2019 | Phase 2 |
J Med Chem.2009 Nov 26;52(22):7170-85.
Differential biochemical trapping of PARP1 by clinical PARP inhibitors.Cancer Res.2012 Nov 1;72(21):5588-99. |
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Three clinical PARP inhibitors differ in their potency to poison PARP1 and PARP2 irrespective of their potency to inhibit PARP catalytic activity.Cancer Res.2012 Nov 1;72(21):5588-99. |
Differential cellular trapping of PARP1 and PARP2 by clinical PARP inhibitors.Cancer Res.2012 Nov 1;72(21):5588-99. |
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