Screen 18 Compounds

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C1.2.3. Pilot Screening of compound library: We will screen a subset of 3,000 CNS active compounds from the Scripps Drug Discovery Library (SDDL) that have been preselected by our collaborators Louis Scampavia and Tim Spicer. As is standard practice at our Molecular Screening Center, we will initially test all compounds in triplicate at a concentration of 10 μM. Factoring in the exclusion of wells at the edge of plates, which are susceptible to edge effects, we can screen 18 compounds on each plate with one negative control and one positive control. We estimate that we can prepare 20 plates (10 for hippocampal and 10 for cortical neurons) and thus screen 180 compounds per week. Once candidates are chosen based on the activation or inhibition of transport (criteria for selection: at least a 10 % change with a p 1 μM and inhibitors. We will first focus on inhibitors with IC50 < 1 μM and then on compounds with IC50 > 1 μM.…show more content…
To guard against problems with compound degradation, cross-contamination or experimenter error the purity and identity of compounds will be assessed by LCMS (liquid Chromatography and Mass Spectrometry) and where possible by 1H and 13C-NMR as previously described18. In addition, compounds will be retesting from powder stocks obtained from commercial sources and if required we will collaborate with Tom Bannister, an experienced medicinal chemist, who will help us with synthesizing

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