Table 1.

AZ-4217 potency against BACE1, related aspartic proteases, and cellular APP processing assays

	Results ± SD
Study
hBACE1 affinity, TR-FRET (Ki)	1.8 ± 0.40 nm
SH-SY5Y/APP, Aβ40 readout (IC50)	200 ± 54 pm
SH-SY5Y, sAPPβ readout (IC50)	160 ± 110 pm
C57BL/6 Mouse Primary Neurons, Aβ40 readout (IC50)	2.7 ± 0.82 nm
Tg2576 mouse primary neurons, Aβ40 readout (IC50)	38 ± 11 nm
Guinea pig primary neurons, Aβ40 readout (IC50)	2.0 ± 1.3 nm
Selectivity targets
hBACE2 affinity, TR-FRET (Ki)	2.6 ± 0.86 nm (no sel. versus hBACE1)
hCathepsin D affinity, TR-FRET (Ki)	25 μm (>10,000x sel. versus hBACE1)

Data are reported as mean ± SD of at least four independent experiments (Cathepsin D only measured twice).