Potent and highly selective Glycogen Synthase Kinase-3β (GSK-3β; Ki value 4.9 nM) inhibitor for Alzheimer’s disease with good BBB permeability in a bovine endothelial cell assay. AZD2858 inhibits GSK-3β-mediated tau phosphorylation (IC50 value 76 nM) in vitro, and shows a good overall selectivity versus a panel of 26 kinases and >100 fold selectivity over CDK2 (Ki value 540 nM).In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass by GSK-3 mediated inhibition of Wnt canonical signaling, making AZD2858 a possible therapeutic candidate for osteoporosis. The free base AZD2858 is available as Axon 3771.

KEYWORDS: AZD2858 hydrochloride | GSK3â inhibitor | GSK3 | GSK-3 | AZD-2858 | AZD-2858 | Wnt | osteoporosis | Alzheimer's | AD | amyloid | tau | CDK2 | glycogen | synthase