Identification and Preclinical Pharmacology of the -Secretase Modulator BMS-869780
BMS-869780 had minimal effect on APP-CTF accumulation in vitro. H4-APPsw cell cultures were treated overnight with the indicated concentrations of BMS-869780, BMS-299897 or vehicle (0.1% DMSO). (a) Cells were harvested and analyzed by western blotting for APP-CTFα, APP-CTFβ, and GAPDH. Lane 1; culture treated with vehicle 0.1% DMSO. Lanes 2–5; cultures treated with BMS-869780 at 100 nM, 300 nM, 1000 nM, or 3000 nM, respectively. Lanes 6–8; cultures treated with BMS-299897 at 30 nM, 100 nM, or 300 nM, respectively. (b) Levels of Aβ1-42 (red; left -axis), Aβ1-40 (green; right -axis), and Aβ1-x (grey; right -axis) were quantified.
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