SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer’s disease (AD) treatment.

GSK-3β (human):12 nM (IC50)

SAR502250 (0.01-1 μM; 36 h) mitigates Aβ25-35-induced cell death in rat embryonic hippocampal neurons[2].

SAR502250, administered in varying dosages and methods, exhibits several notable effects in transgenic mice: it attenuates tau hyperphosphorylation in the cortex and spinal cord (1-100 mg/kg, single p.o.), improves cognitive deficits post-Aβ25-35 infusion (10-30 mg/kg, p.o. once daily for 7 weeks) in APP(SW)/Tau(VLW) mice, increases lever-presses in the IRT bin (49-96s) and reinforced responses (10-30 mg/kg, single p.o.), ameliorates chronic stress-induced coat degradation (30 mg/kg, i.p. once daily for 28 days), and decreases psychostimulant-induced hyperactivity (10-60 mg/kg, single p.o.)[2].