AZD1080 - CAS 612487-72-6
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Not Intended for Therapeutic Use. For research use only.
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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.
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1.AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans.
Georgievska B1, Sandin J, Doherty J, Mörtberg A, Neelissen J, Andersson A, Gruber S, Nilsson Y, Schött P, Arvidsson PI, Hellberg S, Osswald G, Berg S, Fälting J, Bhat RV. J Neurochem. 2013 May;125(3):446-56. doi: 10.1111/jnc.12203. Epub 2013 Mar 11.
Abnormal tau phosphorylation resulting in detachment of tau from microtubules and aggregation are critical events in neuronal dysfunction, degeneration, and neurofibrillary pathology seen in Alzheimer's disease. Glycogen synthase kinase-3β (GSK3β) is a key target for drug discovery in the treatment of Alzheimer's disease and related tauopathies because of its potential to abnormally phosphorylate proteins and contribute to synaptic degeneration. We report the discovery of AZD1080, a potent and selective GSK3 inhibitor that demonstrates peripheral target engagement in Phase 1 clinical studies. AZD1080 inhibits tau phosphorylation in cells expressing human tau and in intact rat brain. Interestingly, subchronic but not acute administration with AZD1080 reverses MK-801-induced deficits, measured by long-term potentiation in hippocampal slices and in a cognitive test in mice, suggesting that reversal of synaptic plasticity deficits in dysfunctional systems requires longer term modifications of proteins downstream of GSK3β signaling.
2.Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer.
Chen S1, Sun KX1, Feng MX1, Sang XB1, Liu BL1, Zhao Y1. Drug Des Devel Ther. 2016 Mar 18;10:1225-32. doi: 10.2147/DDDT.S102506. eCollection 2016.
BACKGROUND: Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines.
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CAS 612487-72-6 AZD1080

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