TCS 2002

GSK-3β inhibitor 9 (Compound 9b) is a highly selective, orally bioavailable and potent GSK-3β inhibitor with the IC50 of 35 nM. GSK-3β inhibitor 9 shows good pharmacokinetic profiles including favorable BBB penetration. GSK-3β inhibitor 9 can be used for the research of Alzheimer’s disease[1].

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Research Areas >> Neurological Disease

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

GSK-3:35 nM (IC50)

GSK-3β inhibitor 9 (Compound 9b) (1-3 mg/kg;1-24 hours; GS rats andC57BL/6N mice) exhibits good pharmacokinetic profiles and favor able BBB permeability with AUC0-24h value is 734 ng•h/g and Kp value (ratio of brain and plasma) is 1.6[1]. Animal Model: IGS rats (male, 8 weeks old)[1] Dosage: 1 and 3mg/kg Administration: Intravenous injection and oral administration;for 1, 2, 4, 8, 24 hours. Result: 1.19 comp (S)-9b (S)-9c VDSS,iv (mL/kg) 1134 1650 CLtotal,iv (mL/min/kg) 27.4 28.4 Cmax,po (ng/mL) 396.9 289.6 AUC0-24 h,po (ng·h/mL) 1380.6 1229.1 MRTpo (h) 2.19 3.03 Fd (%) 72.8 65.5

[1]. Morihisa Saitoh, 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 Oct 22;52(20):6270-86.