MK-8719 (MK8719) is a a highly potent, selective, CNS-penetrable inhibitor of O-GlcNAcase (OGA) with Ki of 7.9 nM (hOGA).
MK-8719 displays no effect against human hexosaminidase A/B (HexA/B) and human N-acetylglucosaminidase (NAGLU), as well as a panel of > 100 receptor and enzyme targets.
MK-8719 inhibits human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog.
MK-8719 produces a dose-dependent increase in O-GlcNAc in PC12 cells with IC50 of 52.7 nM.
MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner in vivo, demonstrateed robust target engagement in the brains of rats and rTg4510 mice.
