TCS 2002 is a potent inhibitor of GSK-3β with IC50 value of 35 nM [1].
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 [1].
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% [1].
Reference:
[1]. Saitoh M, Kunitomo J, Kimura E, et al. 2-{3-[4-(Alkylsulfinyl)phenyl]-1-benzofuran-5-yl}-5-methyl-1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta with good brain permeability. J Med Chem, 2009, 52(20): 6270-6286.