GSK-3β/G9a-IN-1

GSK-3β/G9a-IN-1 (Compound T2) is an orally active, selective inhibitor that penetrates the blood-brain barrier, targeting G9a (substrate-competitive, IC50: 1.1 μM) and GSK-3β (ATP-competitive, IC50: 0.8 μM) . It acts as a potent H3K9me2 inhibitor, facilitating chromatin remodeling and reducing tau protein phosphorylation and Aβ aggregation. Additionally, GSK-3β/G9a-IN-1 inhibits the glucocorticoid receptor, androgen receptor, and alpha-2A adrenergic receptor, and upregulates SAGA complex members such as Eny2 and Sgf29. This compound significantly enhances memory, restores social behavior, and increases synaptic complexity in late-onset Alzheimer's disease.