AZD2858

AZD2858 is a selective GSK-3 inhibitor with IC50 value of 68 nM.
Glycogen synthase kinase 3β (GSK-3β) plays an important role in the canonical Wnt pathway and participates in many biological processes [1].
In human osteoblast cells, AZD2858 increased β-catenin levels in a short time [1]. Incubation of hADSC with AZD2858 led to a significantly increase in osteogenic mineralisation. This indicated that inhibition of GSK-3 enhanced osteogenic differentiation of hADSC [2].
Treatment rats with AZD2858 orally increased trabecular bone mass in a dose-dependent way after a two-week treatment. The significant effect was also seen at cortical sites. Both vertebral compression strength and diaphyseal strength of femora increased in biomechanical testing. Furthermore, there was a dramatic increase in bone formation indices, serum markers of both bone formation and resorption were also elevated [1]. Also, AZD2858 drives mesenchymal cells into osteoblastic cells and leads to direct bone repair in an unstable fracture milieu [3].
References:
[1]. Marsell R, Sisask G, Nilsson Y, et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone, 2012, 50(3): 619-627.
[2]. Gilmour PS, O'Shea PJ, Fagura M, et al. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats. Toxicol Appl Pharmacol, 2013, 272(2): 399-407.
[3]. Sisask G, Marsell R, Sundgren-Andersson A, et al. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone, 2013, 54(1): 126-132.