Lanabecestat (AZD3293) is a highly potent and highly permeable, orally active BACE1 inhibitor (Ki: 0.4 nM) that crosses the blood-brain barrier, Lanabecestat can be used for the study of neurological diseases like Alzheimer's disease.

BACE1:0.4 nM, BACE1:0.4 nM (cell free)

Cells are incubated with different Lanabecestat concentrations for 5 to 16?h, and the release of sAβPPβ, Aβ1-40, Aβ1-42, or sAβPPα into the medium is analyzed using kits. Cytotoxic effect of Lanabecestat is evaluated in the cell plates using cell proliferation/cytotoxicity kit.

Female 7- to 14-week-old C57BL/6 mice (n=6 per treatment group and time point) receive a vehicle or Lanabecestat solution at 50, 100, or 200 μmol/kg (20, 41, or 82?mg/kg) as a single dose via oral gavage. Mice and guinea pigs are anesthetized 1.5, 2, 3, 4, 6, 8, 16, 24, or 48?h after the (last) administration of vehicle or drug and are then kept under isoflurane anesthesia. Cerebrospinal fluid (CSF) is aspirated from the cisterna magna, and plasma is isolated from blood collected by cardiac puncture into EDTA tubes. The animals are then sacrificed by decapitation, and the brains are dissected into hemispheres.