PF-06751979 is a potent, selective, brain penetrant BACE1 inhibitor with binding IC50 of 7.3, 27-fold selectivity over BACE2.
PF-06751979 shows BACE1 inhibition and sAPPβ production in whole-cell assay with IC50 of 5.1 and 5 nM.
PF-06751979 displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2; demonstrates potent and dose-dependent Aβ lowering in human CSF with lacking hypopigmentation compared with AZD3239.
