GSK-3

453.52

DMSO : 7 mg/mL (15.43 mM)

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AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, inhibits tau phosphorylation at the S396 site, activates Wnt signaling pathway. AZD2858 treatment (1 μM, 12 h) on primary isolated human osteoblast-like cells results in a 3-fold increase of β-catenin levels. AZD2858 causes β-catenin stabilisation in human and rat mesenchymal stem cells, stimulates hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro.

In rats, oral AZD2858 treatment causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control). A small but significant effect is also seen at cortical sites (total BMC: 111% of control). AZD285 treatment (30 μmol/kg) on rats daily for up to 3 weeks shows an increase in both mineral density (of 28% at 2 weeks and 38% at 3 weeks) and mineral content (of 81% at 2 weeks and 93% at 3 weeks) in the calluses. AZD285 treatment makes the fractures heals more rapidly, with a bony callus without an obvious endochondral component. AZD2858 produces time-dependent changes in serum bone turnover biomarkers and increases bone mass over 28 days exposure in rats. After 7 days, AZD2858 increases the bone formation biomarker P1NP, and reduces the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats.

C₂₁H₂₃N₇O₃S

486424-20-8