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Table 1 In-vitro Properties of Gamma-Secretase Inhibitors

From: Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease

Compound gamma:APP IC50 (nM) gamma:Notch IC50 (nM) enzyme selectivity (APP/Notch) SNC Aβ EC50 (nM) SNC Notch Signaling EC50 (nM) Cellular Selectivity (APP/Notch)
L-685,458 0.63 (1) nd NA 13.2 ± 4.5 (4) 184 ± 145 (3) 14
LY411575 0.035 (1) 0.082 ± 0.008 (3) 2.4 0.116 ± 0.011 (3) 1.8 ± 1.35 (3) 16
ELN158162 650 14,000 21.5 nd nd NA
ELN318463 37.2 ± 18 (51) 1,889 ± 722 (3) 51 23.4 ± 8.6 (10) 2,818 ± 670 (10) 120
ELN475516 2.06 ± 0.35 (16) 29.81 ± 2.59 (4) 14.5 8.73 ± 3.96 (298) 719 ± 224.6 (298) 82
  1. Potency For Inhibition Of App And Notch Processing by select gamma-secretase inhibitors in enzyme, as well as cellular assays described in text. The value in parentheses next to each IC50 indicates the number of independent test occasions used to derive the IC50 value. Note: Cellular selectivity of L-685,458 was determined prior to development of the SNC assay using different cellular assays for Aβ production and Notch signaling.
  2. Abbreviations: APP, amyloid precursor protein; SNC, a stable CHO cell line co-expressing APPS w, rat N otchΔE, and an NICD responsive C BF-Luciferase reporter gene used to simultaneously assay inhibition of Aβ production, and Notch signaling; Aβ, amyloid beta-peptide.