Potency of LY2886721 in BACE1 and other aspartyl proteases and potency of LY2886721 in cellular assays
| Aspartyl protease assays, absolute IC50, nm (SD) | |||||
| hBACE1 mca FRET assay (n = 10): 20.3 (10.1) | hBACE2 mca FRET assay (n = 12/14): 10.2 (4.8) | Cathepsin D FRET assay (n = 1/6): >300,000 | Pepsin FRET assay (n = 5): >100,000 | Renin FRET assay (n = 6): >100,000 | |
| Cellular assays, relative IC50, nm (SD) | |||||
| HEK293Swe Aβ1–40 (n = 9): 18.5 (12.7) | HEK293Swe Aβ1–42 (n = 10): 19.7 (10.3) | HEK293Swe cytotox (n = 1/9): >100,000 | PDAPP 1o neuron Aβ1–40 (n = 6): 10.7 (3.5) | PDAPP 1o neuron Aβ1–42 (n = 6): 9.2 (3.9) | PDAPP 1o neuron cytotox (n = 1/6): >50,000 |
hBACE1, human recombinant beta-APP cleaving enzyme1; hBACE2, human recombinant beta-APP cleaving enzyme 2; IC50, concentration at which enzyme activity is inhibited by 50%; mca, methylcoumarin.