Identification and Preclinical Pharmacology of the -Secretase Modulator BMS-869780
Figure 1
(a) Chemical structures of the compounds used in this study are shown. (b) Overview of the HTS and subsequent triage of compounds summarizes experimentation steps in boxes, with outcomes indicated beside the arrows. Costs of reagents and disposables were a major consideration in the design, particularly the initial screen of 106 samples. (c) Principle of the A1-42 immunoassay; simultaneous binding of monoclonal antibody conjugates 252-APC and 565-Eu (specific for C-terminus of A1-42) to A1-42 leads to FRET-based emission at 665 nm. The ratio of emission at 665 nm to fluorescence at 615 nm represents the level of A1-42 in the sample. (d) Principle of the A1-40 immunoassay; same as described above for the A1-42 immunoassay, except that the monoclonal antibody conjugate TSD-Eu (specific for C-terminus of A1-40) was used in place of 565-Eu.