Browsing by Subject "High-Throughput screening"

It is well known that the central nervous system is a highly isolated tissue. Because of this the physico-chemical criteria to be met by an orally administered central nervous system drug are very strict. This work describes methods that can be used to select drug candidates and screening collections that have a higher possibility of being relevant to central nervous system drug development projects. This work also argues that small molecular space is so vast that it is difficult to imagine any progress without focusing screening collections in some way or another. Given that most available commercial compounds are very similar in some respects, it is very much possible that this presents a bottle-neck for the progress of drug development as a whole. Therefore, research on novel methods for compound production are also evaluated. In addition, this work describes the miniaturization and automation of a previously published ELISA-based assay. This assay measures the activation of a tyrosine kinase receptor (TrkB), expressed in a fibroblast cell line. The receptor, and it's endogenous ligand, Brain-derived neurotrophic factor, have been linked to the mechanism of action of previously discovered medical interventions used in the treatment of depression. Such an assay can be used to discover either small molecule agonists or antagonists acting upon the receptor. These molecules could possibly be clinically relevant in the treatment of depressive disorders and anxiety. It is demonstrated that it is indeed possible to miniaturize and automate the method, making it significantly more suitable for high-throughput screening. The original method was carried out in 24-well plates, transferring the samples to another plate for measurement. The new design uses 96-well plates and performs the entire process on the same plate.