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 |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related GSK-3 Products |
|---|
| Phospho-Glycogen Synthase Peptide-2(substrate)
Phospho-Glycogen Synthase Peptide-2 (substrate) is peptide substrate for glycogen synthase kinase-3 (GSK-3) and can be used for affinity purification of protein-serine kinases. |
| FRATtide
FRATtide is a peptide derived from the GSK-3 binding protein that inhibits the phosphorylation of Axin and β-catenin. |
| ZDWX-25
ZDWX-25 is a highly potent GSK-3β and DYRK1A dual inhibitor with an IC50 value of 71 nM for GSK-3β. |
| TC-G 24
TC-G 24 is a potent, selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 17.1 nM. |
| SAR502250
SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. |
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