Figure 3
From: Pharmacological targeting of the β-amyloid precursor protein intracellular domain
The photoactivatable CHF5074-BpB derivative retains the γ-secretase modulatory properties of the parent compound.
(a) Chemical structure of the benzophenone-biotin (BpB) derivative of CHF5074, whose synthesis is described in Supplementary Methods. Similar to the parent compound, CHF5074-BpB reduced Aβ40 and Aβ42 secretion (b) and increased Aβ38 production (cf. data reported in Supplementary Fig. S1a and S1b) (c). Aβ peptide release was evaluated by ELISAs performed on conditioned culture media from H4swe cells exposed to the indicated concentrations of CHF5074-BpB (0.1–100 μM) for 18 hours. Data are percentages of control ± s.e.m. from three independent experiments. (d) Representative results obtained from immunoblot analysis (anti-APP C-terminus and control anti-actin antibodies as in Fig. 2c) of extracts from H4swe cells treated with vehicle or CHF5074-BpB (1–100 μM). Full-length blots were presented in Supplementary Figure S4. (e) Cell viability, assayed with the lactate dehydrogenase (LDH) release assay, was not appreciably affected by CHF5074-BpB at any of the tested concentrations; data are presented as percentages of control ± s.e.m. from three independent experiments.
