A 100K well screen for a muscarinic receptor using the Epic^® label-free system – a reflection on the benefits of the label-free approach to screening seven-transmembrane receptors

Abstract

Seven-transmembrane receptors (7TMRs) are a family of proteins of great interest as therapeutic targets because of their abundance on the cell surface, diverse effects in modulating cell behavior and success as a key class of drugs. We have evaluated the Epic^® label-free system for the purpose of identifying antagonists of the muscarinic M3 receptor. We compared the data generated from the label-free technology with data for the same compounds in a calcium flux assay. We have shown that this technology can be used for high throughput screening (HTS) of 7TMRs and as an orthogonal approach to enable rapid evaluation of HTS outputs. A number of compounds have been identified which were not found in a functional HTS measuring the output from a single pathway, which may offer new approaches to inhibiting responses through this receptor.

Keywords::

• Label-free
• signaling
• seven-transmembrane receptor
• high throughput screening

Acknowledgement

Declaration of interest: We would like to acknowledge the assistance of Andy Kirk and Helen Edwards (AZ Charnwood) in generating the radioligand binding data. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.