LY-2811376 is a orally-available, non-peptidic inhibitor of hBACE1 with an IC50 of 239 nM. Selectivity of LY-2811376 for BACE1 over BACE2 was found to be 10-fold, and 50-fold or greater over related aspartyl proteases cathepsin D, pepsin, or renin. [1] In APP-overexpressing human embryonic kidney cell lines, LY-2811376 treatment decreased Ab secretion in a concentration-dependent fashion, with an EC50 of ~300 nM. In primary neuronal cultures of PDAPP transgenic mouse, Ab secretion was measured at an EC50 of ~100 nM.

In vivo, LY2811376 inhibits BACE1 activity by concomitantly reducing C99 and sAPPb, the two primary APP cleavage products generated by BACE1.