A-966492
For research use only.
Catalog No.S2197
6 publications

CAS No. 934162-61-5
A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively.
2 Customer Reviews
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Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band.
Nat Methods 2013 10(10), 981-4. A-966492 purchased from Selleck.
Analysis of four PARP inhibitor A-966492 and its correlation with olaparib. Plots of log2(compound/control) values (or median values if identified multiple times) of the intensity of ADP-ribosylated peptides identified using olaparib and AG14361. Only peptides with all modification sites confidently localized (MOD score ≥13) are included. Ctrl, control.
Nat Methods 2013 10(10), 981-4. A-966492 purchased from Selleck.
Purity & Quality Control
Choose Selective PARP Inhibitors
Biological Activity
Description | A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively. | ||||||||||||||||
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Features | A promising, structurally diverse benzimidazole analogue that is being further characterized preclinically. | ||||||||||||||||
Targets |
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In vitro |
A-966492 is one of the most potent PARP inhibitors. A-966492 displays excellent potency against the PARP-1 enzyme with a Kiof 1 nM and an EC50 of 1 nM in a whole cell assay. A-966492 significantly enhances the efficacy of TMZ in a dose-dependent manner. In addition, A-966492 is orally bioavailable across multiple species, crosses the blood−brain barrier, and appears to distribute into tumor tissue. A-966492 represents a promising, structurally diverse benzimidazole analogue and is being further characterized preclinically. [1] |
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Cell Data |
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In vivo | A-966492 also demonstrates good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin. In addition, A-966492 has excellent pharmaceutical properties and has demonstrated in vivo efficacy in preclinical mouse tumor models in combination with TMZ and carboplatin, as well as single agent activity in a BRCA1-deficient MX-1 tumor model. A-966492 is further characterized in Sprague−Dawley rats, beagle dogs, and cynomolgus monkeys, with A-966492 demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours. In vivo, A-966492 demonstrates significant enhancement of the efficacy of TMZ in a murine B16F10 syngeneic melanoma model, with the A-966492 combination groups showing superior efficacy. [1] |
Protocol
Kinase Assay: |
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PARP Enzyme Assay: The enzyme assay is conducted in buffer containing 50 mM Tris, pH 8.0, 1 mM dithiothreitol(DTT), and 4 mM MgCl2. PARP reactions contains 1.5 μM [3H]-NAD+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Autoreactions utilizing SPA bead-based detection are carried out in 100 μL volumes in white 96-well plates. Reactions are initiated by adding 50 μL of 2X NAD+ substrate mixture to 50 μL of 2× enzyme mixture containing PARP and DNA. These reactions are terminated by the addition of 150 μL of 1.5 mM benzamide (∼1 × 103-fold over its IC50). A 170 μL amount of the stopped reaction mixtures is transferred to streptavidin-coated Flash Plates, incubated for 1 hour, and counted using a TopCount microplate scintillation counter. Ki data are determined from inhibition curves at various substrate concentrations. |
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Cell Research: |
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Animal Research: |
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Solubility (25°C)
In vitro | DMSO | 64 mg/mL warmed (197.31 mM) |
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Water | Insoluble | |
Ethanol | Insoluble |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
Molecular Weight | 324.35 |
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Formula | C18H17FN4O |
CAS No. | 934162-61-5 |
Storage |
powder in solvent |
Synonyms | N/A |
Smiles | C1CC(NC1)C2=CC(=C(C=C2)C3=NC4=C(C=CC=C4N3)C(=O)N)F |
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment) | ||||||||||
Dosage | mg/kg | Average weight of animals | g | Dosing volume per animal | ul | Number of animals | ||||
Step 2: Enter the in vivo formulation () | ||||||||||
% DMSO % % Tween 80 % ddH2O | ||||||||||
CalculateReset |
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: : mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL,)
Method for preparing in vivo formulation:Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80,mix and clarify, next add μL ddH2O,mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Bio Calculators
Molarity Calculator
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Dilution Calculator
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Molarity Calculator
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.
Frequently Asked Questions
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Question 1:
how long is a half-life of A966492 drug?
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Answer:
Sorry, Selleck don't have such information of this compound. But based on the reference: http://www.ncbi.nlm.nih.gov/pubmed/20337371, A966492 may have half-life of 1.7−1.9 hours. “with A-966492 demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours (in vivo)” which is cited from the reference.