AZD1080 is a selective,orally active,brain permeableGSK3inhibitor,inhibits human GSK3α and GSK3β withKiof 6.9 nM and 31 nM,respectively,shows>14-fold selectivity against CDK2,CDK5,CDK1 and Erk2.
生化机理
Description: IC50 Value:31 nM[1] AZD1080 is a potent and selective GSK3 inhibitor that demonstrates peripheral target engagement in Phase 1 clinical studies. in vitro:AZD1080 inhibits tau phosphorylation in cells expressing human tau and in intact rat brain.Interestingly,subchronic but not acute administration with AZD1080 reverses MK-801-induced deficits,measured by long-term potentiation in hippocampal slices and in a cognitive test in mice,suggesting that reversal of synaptic plasticity deficits in dysfunctional systems requires longer term modifications of proteins downstream of GSK3βsignaling[1]. in vivo:AZD1080 reverses MK-801-induced impairments in mouse model of cognition.AZD1080 treatment significantly prevents MK-801-induced deficits at both time-points(*p<0.05;**p<0.01).Data are presented as mean _ SEM(n = 9-12 subjects/group).[1] Clinical trial:Phase 1