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A-966492 PARP inhibitor

Name: A-966492
Brand: Selleck Chemicals
SKU: S2197
Availability: InStock
Rating: 5 (9 reviews)

Cat.No.S2197

A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with K_i of 1 nM and 1.5 nM, respectively.

Chemical Structure

Molecular Weight: 324.35

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.98%

99.98

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
C41 cells	Function assay				Inhibition of PARP1 in human C41 cells by FITC-conjugated DAPI staining, EC50=0.001 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	324.35	Formula	C₁₈H₁₇FN₄O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	934162-61-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1CC(NC1)C2=CC(=C(C=C2)C3=NC4=C(C=CC=C4N3)C(=O)N)F

Solubility

In vitro
Batch:

DMSO : 33 mg/mL (101.74 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (30.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (30.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

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:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 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.

Mechanism of Action

Features	A promising, structurally diverse benzimidazole analogue that is being further characterized preclinically.
Targets/IC₅₀/Ki	PARP1 ^[1] (Cell-free assay) 1 nM(Ki) PARP1 ^[1] (a whole cell assay) 1 nM(EC50) PARP2 ^[1] (Cell-free assay) 1.5 nM(Ki)
In vitro	A-966492 is one of the most potent PARP inhibitors. This compound displays excellent potency against the PARP-1 enzyme with a K_iof 1 nM and an EC50 of 1 nM in a whole cell assay. It significantly enhances the efficacy of TMZ in a dose-dependent manner. In addition, this chemical is orally bioavailable across multiple species, crosses the blood−brain barrier, and appears to distribute into tumor tissue. It represents a promising, structurally diverse benzimidazole analogue and is being further characterized preclinically. ^[1]
Kinase Assay	PARP Enzyme Assay
Kinase 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. K_i data are determined from inhibition curves at various substrate concentrations.
In vivo	A-966492 also demonstrates good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination and in an MX-1 breast cancer xenograft model both as a single agent and in combination. In addition, this compound has excellent pharmaceutical properties and has demonstrated in vivo efficacy in preclinical mouse tumor models in combination with TMZ, as well as single agent activity in a BRCA1-deficient MX-1 tumor model. It is further characterized in Sprague−Dawley rats, beagle dogs, and cynomolgus monkeys, with this chemical demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours. In vivo, it demonstrates significant enhancement of the efficacy of TMZ in a murine B16F10 syngeneic melanoma model, with the combination groups showing superior efficacy. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/20337371/

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Handling Instructions

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Frequently Asked Questions

Question 1:
What is the half-life of this compound?

Answer:
Sorry, Selleck don't have such information of this compound. But based on the reference: http://www.ncbi.nlm.nih.gov/pubmed/20337371, it may have half-life of 1.7−1.9 hours. “with this compound demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours (in vivo)” which is cited from the reference.

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