AZD1080

AZD1080 is a potent, selective, orally active, brain‑penetrant small‑molecule inhibitor of glycogen synthase kinase‑3 (GSK3), originally developed by AstraZeneca for Alzheimer’s disease and other neurodegenerative indications. It inhibits recombinant human GSK3α and GSK3β with low‑nanomolar affinity and binds the ATP site of GSK3β, leading to reduced phosphorylation of tau and downstream substrates in cells and rodent brain, with reversal of MK‑801–induced synaptic plasticity and cognitive deficits in preclinical models.[2][3][5][12][13] In Phase 1 multiple‑ascending‑dose studies in healthy volunteers, AZD1080 showed peripheral target engagement via sustained suppression of glycogen synthase activity in blood mononuclear cells, but development in Alzheimer’s disease was not advanced beyond early clinical testing.[2][5][9][11] More recently, AZD1080 has been studied preclinically as an anti‑tumor agent, where GSK3β inhibition suppresses cancer stem‑cell stemness, invasion, and malignant behavior in ovarian cancer and osteosarcoma models, supporting its use as a tool compound and potential therapeutic lead in oncology.[3][6]