TCS 2002 is a potent inhibitor of GSK-3β with IC50 value of 35 nM . Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase and functions by phosphorylating a serine or threonine residue on its target protein. GSK3β plays an important role in neuronal cell development, energy metabolism and body pattern formation. TCS 2002 is a potent GSK -3β inhibitor with IC50 value of 35 nM. (S) -TCS 2002 and (R) -TCS 2002 inhibited GSK-3β with IC50 values of 34 and 140 nM, respectively. TCS 2002 exhibited good bioavailability (F=40%) and solubility (38 μg/mL). (S) -TCS 2002 showed no inhibitory activity against 12 tyrosine kinases and 10 serine/threonine kinases up to 10 μM, indicating that (S) -TCS 2002 was a highly selective GSK -3β inhibitor . In mice, cold water stress (CWS) induced tau hyperphosphorylation at several GSK -3β directed sites such as S199, Thr205, Thr231 and Ser396. (S) -TCS 2002 significantly inhibited tau phosphorylation by 35% .