For research use only.
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.
Selleck's A-966492 has been cited by 5 publications
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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.
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|Description||A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively.|
|Features||A promising, structurally diverse benzimidazole analogue that is being further characterized preclinically.|
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. 
|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. |
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.
|In vitro||DMSO||64 mg/mL warmed (197.31 mM)|
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Frequently Asked Questions
how long is a half-life of A966492 drug?
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.