AZD2858 - CAS 486424-20-8
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Not Intended for Therapeutic Use. For research use only.
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Potent and highly selective Glycogen Synthase Kinase-3β (GSK3β; Ki value 4.9 nM) inhibitor for Alzheimer’s disease with good BBB permeability in a bovine endothelial cell assay. AZD 2858 inhibits GSK3β-mediated tau phosphorylation (IC50 value 76 nM) in vitro, and shows a good overall selectivity versus a panel of 26 kinases and >100 fold selectivity over CDK2 (Ki value 540 nM).In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass by GSK3 mediated inhibition of Wnt canonical signaling, making AZD2858 a possible therapeutic candidate for osteoporosis.
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1.Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation.
Sisask G1, Marsell R, Sundgren-Andersson A, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. Bone. 2013 May;54(1):126-32. doi: 10.1016/j.bone.2013.01.019. Epub 2013 Jan 19.
Fracture healing is a complex interplay between endochondral and intramembranous bone formation processes. The canonical Wnt/β-catenin pathway enhances new bone formation and may play a role in fracture healing. Glycogen synthase kinase 3β (GSK3β) is a key regulator of β-catenin degradation. In this study, we investigate the effects of AZD2858, an orally bioactive GSK3 inhibitor, on fracture healing. Femoral fractures were produced in rats after the insertion of a femoral nail. The rats were treated with oral administration of AZD2858 at a dose of 30 μmol/kg (20mg/kg) daily for up to 3 weeks, while control animals were administered vehicle. At 4days, and at 1, 2 and 3 weeks, histological analysis was performed, and at the 2 and 3 week time points, we performed peripheral quantitative computed tomography (pQCT), X-rays, and four-point bending tests. Peripheral QCT showed an increase in both mineral density (of 28% at 2 weeks and 38% at 3weeks) and mineral content (of 81% at 2 weeks and 93% at 3 weeks) in the calluses from AZD2858 treated animals as compared to vehicle treated animals.
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CAS 486424-20-8 AZD2858

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