A TR-FRET approach to measure the kinetics of ligand-receptor binding and its application of fragment screening

In the drug discovery process, the kinetics of ligand-receptor binding and binding affinities are usually studied at a late time point. This is mostly because of technical difficulties and the relative low-throughput that current assays provide. 

However, optimizing receptor binding kinetics can be highly beneficial for drug discovery. Efficacy can be improved through the insurmountable antagonism of dynamic physiological systems, as well as duration of action can be prolonged. Moreover, binding kinetics seem to play a role biased agonism.

In this scientific talk, the potential clinical benefits of binding kinetics optimization are introduced. Current methods for measuring kinetic parameters are reviewed as well.

A novel approach capable of simultaneously detecting the kinetics of multiple compounds is described. This approach relies on TR-FRET kinetic detection and enables the use of kinetics assays for screening purposes. It also supports the kinetic detection of compounds with low affinity. 

This is demonstrated by the description of a recently run dopamine D2 receptor fragment screening campaign.

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