AZD1080

Catalog No.S7145 Batch:S714502

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Technical Data

Formula

C19H18N4O2
Molecular Weight 334.37 CAS No. 612487-72-6
Solubility (25°C)* In vitro DMSO 66 mg/mL (197.38 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol
20.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of clarified PEG400 stock solution of 66.67 mg/ml to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O Dilute to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with Ki of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against CDK2, CDK5, CDK1 and Erk2.
Targets
GSK-3α [1]
(Cell-free assay)		 GSK-3β [1]
(Cell-free assay)
6.9 nM 31 nM
In vitro AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against cdk2, cdk5, cdk1 and Erk2. AZD1080 inhibits tau phosphorylation in cells expressing human tau, with IC50 of 324 nM. [1]
In vivo AZD1080 inhibits tau phosphorylation in rat brain after oral dministration, with brain/plasma exposure ratio of 0.5 – 0.8 at peak concentrations. AZD1080 reverses cognitive deficits and rescues dysfunctional synapses in mice. Acute oral treatment with AZD1080 inhibits peripheral GSK3 activity, produces a dose-dependent reduction of the phosphorylated to total glycogen synthase (GS) ratio, with a mean maximal inhibitory effect of 49% at the highest dose (10 μmol/kg) at 2 h after dosing. [1]
Features A brain permeable GSK3 inhibitor.

Protocol (from reference)

Kinase Assay:[1]
  • Kinase Assay

    GSK3 scintillation proximity assay is done. The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor in clear-bottomed microtiter plates. The biotinylated peptide substrate biotin-AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 12 mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β-mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serum albumin/25 μl and preincubated for 10–15 min. The reaction is initiated by the addition of 0.04 μCi of [γ-33P]ATP and unlabeled ATP in 50 mM Mg(Ac)2 to a final concentration of 1 μM ATP and assay volume of 25 μl. Blank controls without peptide substrate are used. After incubation for 20 min at room temperature, each reaction is terminated by the addition of 25 μl of stop solution containing 5 mM EDTA, 50 μM ATP, 0.1% Triton X-100, and 0.25 mg of streptavidin-coated SPA beads corresponding to 35 pmol of binding capacity. After 6 h the radioactivity is determined in a liquid scintillation counter.
Cell Assay:[1]
  • Cell lines

    3T3 fibroblasts stably expressing 4-repeat human tau

  • Concentrations

    ~20mM

  • Incubation Time

    0-8 h

  • Method

    3T3 fibroblasts are engineered to stably express four-repeat tau protein. These cells have high endogenous levels of GSK3 that is able to phosphorylate tau protein constitutively. This phosphorylation is inhibited by LiCl. After treatment with different compounds, cultures are washed twice with 5 mM MgCl2-PBS. Extracts for Western blot analysis are prepared by homogenizing cells in ice-cold extraction buffer consisting of 20 mM HEPES, pH 7.4, 100 mM NaCl, 10 mM NaF, 1% Triton X-100, 1 mM sodium orthovanadate, 10 mM EDTA, and protease inhibitors (2 mM phenylmethylsulfonyl fluoride, 10 μg/ml aprotinin, 10 μg/ml leupeptin, and 10 μg/ml pepstatin). The samples are homogenized at 4 °C, and protein content is determined by Bradford method. Total protein (25 μg) is electrophoresed on 10% SDS-PAGE gel and transferred to a nitrocellulose membrane. The experiments are performed using the following primary antibodies: tau Ser(P)-396, 1:1000; Tau5, 1:1000; and anti-GSK3β, 1:1000. The filters are incubated with the antibody at 4 °C overnight in 5% nonfat dried milk. A secondary antibody (1:5000), followed by ECL detection reagents are used for immunodetection. Quantitation of immunoreactivity is performed by densitometric scanning.
Animal Study:[1]
  • Animal Models

    C57BL/6 mice

  • Dosages

    3 or 10 μmol/kg, 6 mL/kg

  • Administration

    oral gavage

Selleck's AZD1080 has been cited by 6 publications

Temporal activation of WNT/β-catenin signaling is sufficient to inhibit SOX10 expression and block melanoma growth. [ Oncogene, 2020, 39(20):4132-4154] PubMed: 32238882
Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches [ Int J Mol Sci, 2020, 21(18)E6826] PubMed: 32957634
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors. [ Nat Commun, 2018, 9(1):5154] PubMed: 30514931
Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation. [ Cell Death Dis, 2018, 9(5):504] PubMed: 29724995
Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein [ Aging Cell, 2016, 15(5):914-23] PubMed: 27406053

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.