AZD1080

SKU: orb1307560

Description

AZD1080 is a potent, selective, and brain-penetrant inhibitor of GSK3. It is an orally active small molecule utilized in research to investigate GSK3's role in neurological disorders, including Alzheimer's disease, as demonstrated in both cellular and animal models.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 612487-72-6
• MW: 334.37
• Purity: 99.68% (May vary between batches)
• Formula: C₁₉H₁₈N₄O₂
• SMILES: Oc1[nH]c2ccc(cc2c1-c1ccc(CN2CCOCC2)cn1)C#N
• Target: GSK-3
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.98 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:40 mg/mL (119.63 mM)

Bioactivity

• Target IC50:
  CDK2:5.9 (pKi)|GSK-3β:31 nM|cdk1:5.7 (pKi)|GSK-3α:6.9 nM|cdk5:6.4 (pKi)
• In Vivo:
  AZD1080 inhibits tau phosphorylation in cells expressing human tau with an IC50 of 324 nM. It also inhibits human GSK3α and GSK3β with Ki values of 6.9 nM and 31 nM, respectively, demonstrating over 14-fold selectivity against cdk2, cdk5, cdk1, and Erk2.
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• In Vitro:
  AZD1080 reverses cognitive deficits in mice and rescues their dysfunctional synapses. Oral administration of AZD1080 inhibits tau protein phosphorylation in the rat brain, with a peak brain/plasma exposure ratio of 0.5-0.8. Acute oral intake of AZD1080 suppresses peripheral GSK3 activity in a dose-dependent manner, reducing the phosphorylation ratio of glycogen synthase to total glycogen synthase, achieving an average maximum inhibition of 49% at the highest dose of 10mol/kg.
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• Cell Research:
  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.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, Glycogen synthase kinase 3, Glycogen synthase kinase-3, GSK3, GSK-3, GSK-3α, GSK-3β, AZD1080, AZD-1080, AZD 1080

Compound Identifiers

PubChem CID

135564570