Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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Other Sizes |
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Purity: ≥98%
Niraparib metabolite M1 is a carboxylic acid metabolite of niraparib (MK4827; Zejula), which is a PARP1/2 inhibitor approved for cancer treatment.
Targets |
Niraparib metabolite
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ln Vitro |
Niraparib metabolite M1 has the validation in plasma and urine for the support of clinical studies such as the mass balance research and the absolute bioavailability study[1].
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ln Vivo |
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Animal Protocol |
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References | |||
Additional Infomation |
Niraparib (MK-4827) is a novel poly(ADP-Ribose) polymerase (PARP) inhibitor currently investigated in phase III clinical trials to treat cancers. The development of a new drug includes the characterisation of absorption, metabolism and excretion (AME) of the compound. AME studies are a requirement of regulatory agencies and for this purpose bioanalytical assays are essential. This article describes the development and validation of a bioanalytical assay for niraparib and its carboxylic acid metabolite M1 in human plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample pre-treatment involved protein precipitation for plasma and dilution of urine samples using acetonitrile-methanol (50:50, v/v). Final extracts were injected onto a SunFire C18 column and gradient elution using 20mM ammonium acetate (mobile phase A) and formic acid:acetonitrile:methanol (0.1:50:50, v/v/v) (mobile phase B) was applied. Detection was performed on an API5500 tandem mass spectrometer operating in the positive electrospray ionisation mode applying multiple reaction monitoring (MRM). The assay was successfully validated in accordance with the Food and Drug Administration and latest European Medicines Agency guidelines on bioanalytical method validation and can therefore be applied in pharmacological clinical studies. [1]
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Molecular Formula |
C₁₉H₁₉N₃O₂
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Molecular Weight |
321.37
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Exact Mass |
321.147
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CAS # |
1476777-06-6
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Related CAS # |
Niraparib;1038915-60-4
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PubChem CID |
118737587
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Appearance |
Light brown to brown solid powder
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Density |
1.3±0.1 g/cm3
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Boiling Point |
442.0±45.0 °C at 760 mmHg
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Flash Point |
221.1±28.7 °C
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Vapour Pressure |
0.0±1.1 mmHg at 25°C
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Index of Refraction |
1.693
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LogP |
4.01
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Hydrogen Bond Donor Count |
2
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Hydrogen Bond Acceptor Count |
4
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Rotatable Bond Count |
3
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Heavy Atom Count |
24
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Complexity |
450
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Defined Atom Stereocenter Count |
1
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SMILES |
C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)O
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InChi Key |
HDQHGRLURKGIFL-CQSZACIVSA-N
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InChi Code |
InChI=1S/C19H19N3O2/c23-19(24)17-5-1-3-15-12-22(21-18(15)17)16-8-6-13(7-9-16)14-4-2-10-20-11-14/h1,3,5-9,12,14,20H,2,4,10-11H2,(H,23,24)/t14-/m1/s1
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Chemical Name |
2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxylic acid
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Synonyms |
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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 |
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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: ≥ 2.75 mg/mL (8.56 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 27.5 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: ≥ 2.75 mg/mL (8.56 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 27.5 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: ≥ 2.75 mg/mL (8.56 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 | 3.1117 mL | 15.5584 mL | 31.1168 mL | |
5 mM | 0.6223 mL | 3.1117 mL | 6.2234 mL | |
10 mM | 0.3112 mL | 1.5558 mL | 3.1117 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.
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. th> |
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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. td> |
Differential cellular trapping of PARP1 and PARP2 by clinical PARP inhibitors.Cancer Res.2012 Nov 1;72(21):5588-99. td> |