PROTACGSK-3β Degrader-1 (compound 1) is a degrader targeting GSK-3β with an IC50 of 833 nM. This compound consists of SB-216763 (a GSK-3β inhibitor), a PEG linker, and CRBN (E3 ligase ligand). It reduces neurotoxicity induced by Aβ25-35 peptide and CuSO4 and is applicable in Alzheimer's disease research.

GSK-3β:833 nM

PROTAC GSK-3β Degrader-1 exhibits low cytotoxicity in SH-SY5Y cells at low concentrations (1.25-40 μM, 24 h), but becomes cytotoxic above 20 μM. At 1 μM for 24 hours, it counteracts neurotoxicity induced by CuSO4 (150 μM) in SH-SY5Y cells. Additionally, at concentrations of 0.5-1 μM for 2 hours, it significantly reduces Aβ 25-35 peptide-induced neurotoxicity in a dose-dependent manner. PROTAC GSK-3β Degrader-1 also decreases GSK-3β protein levels in SH-SY5Y cells dose-dependently (0.5-10 μM, 48 h) with a DC50 of 6.22 μM, and at 10 μM for 24 hours, it degrades GSK-3β protein via the UPS pathway.