Table 1.

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

Results ± SD
    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).