Brief Description

AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, inhibits tau phosphorylation at the S396 site, activates Wnt signaling pathway.
IC50 Value: 68 nM [1]
Target: GSK3
in vitro: Treatment (1 μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. AZD2858 treatment (1 μM, 12 h) on primary isolated human osteoblast-like cells results in a 3-fold increase of β-catenin levels [1].
in vivo: 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). A small but significant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increase in both vertebral compression strength at a dose of 20 mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphyseal strength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01) [1]. 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 [2].
References on AZD2858:
[1]. Marsell R, et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone. 2012 Mar;50(3):619-27.
[2]. Sisask G, et al. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone. 2013 May;54(1):126-32.

Solubility

DMSO 7 mg/mL; Water <1 mg/mL; Ethanol <1mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light green to green solid