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AZD2858 is a potent orally active glycogen synthase kinase 3 (GSK-3) inhibitor. AZD2858 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. AZD2858 caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. Treatment (1 μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. In rats, oral AZD2858 treatment caused 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; p<0.001).
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Source | Biochem Biophys Res Commun (2014). Figure 4. AZD2858 |
| Method | PRC | |
| Cell Lines | U2OS cells | |
| Concentrations | 25 and 40 μM | |
| Incubation Time | 24 h | |
| Results | As observed with CCCP, AZD2858 induced PRC(FL), a result consistent with the negative control of PRC expression by GSK-3. |
| Molecular Weight | 453.52 |
| Formula | C21H23N7O3S |
| CAS Number | 486424-20-8 |
| Solubility (25°C) | DMSO 7 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related GSK-3 Products |
|---|
| CHIR-99021
CHIR-99021 (CT99021) is an aminopyrimidine derivative that inhibits GSK3α and GSK3β with IC50 values of 10 and 6.7 nM, respectively. |
| CHIR-99021 HCl
CHIR-99021 HCl (Laduviglusib; CT99021) is a hydrochloride of CHIR-99021, with IC50 of 10 nM and 6.7 nM for GSK-3α and GSK-3β, respectively. |
| SB 216763
SB 216763 is a potent and selective, cell permeable glycogen synthase kinase-3 (GSK-3) inhibitor with an IC50 value of 34 nM for GSK-3α. |
| Indirubin
Indirubin is a potent cyclin-dependent kinases and GSK-3β inhibitor with IC50 of ~75 nM and 0.19 μM. |
| TWS119
TWS119 is a GSK-3β inhibitor with IC50 of 30 nM. |
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