Figure 2

EVP-0015962 is a potent γ-secretase modulator. A. Concentration response curves for Aβ₄₂, Aβ₃₈, and Aβ_Total determined by enzyme-linked immunosorbent assay (ELISA), and for cell viability in the H4-APP₇₅₁ cell assay. IC₅₀ = 67 nM for Aβ₄₂ and EC₅₀ = 33 nM for Aβ₃₈. For cell viability determined using the MTS assay, IC₅₀ = 5.56 μM. IC₅₀ > 3 μM for Aβ_Total. For Aβ₃₈, the EC₅₀ value is determined for the concentration range of 3 nM to 1 μM of EVP-0015962, to avoid the portion of the curve where toxicity is observed. N = 6 independent experiments. B. Concentration response curves for Aβ₄₂, Aβ₃₈, and Aβ_1-x determined by ELISA in media and for MTS from rat primary neocortical cultures. IC₅₀ = 427 nM for Aβ₄₂ and EC₅₀ = 384 nM for Aβ₃₈. IC₅₀ > 30 μM for Aβ_1-x and the MTS assay. N = 4 independent experiments for Aβ₄₂, Aβ_1-x, and MTS and 2 for Aβ₃₈. C. Concentration response curve for Aβ₄₂ in the cell-free assay. IC₅₀ = 3.9 μM. D. Concentration response curve for Aβ₄₀ in the cell-free assay. In the cell-free assays, Aβ was determined by AlphaLisa in triplicate. All data are expressed as mean ± standard error of the mean (SEM). For some data points, error bars are smaller than the sizes of the data points.