Transient Receptor Potential Melastatin 5 (TRPM5) is an intracellular calcium-activated cation-selective ion channel which is expressed in a variety of cells and tissues. Dysfunction of the TRPM5 channel has been linked to a number of pathological conditions including diabetes, inflammatory responses, enteric infections and parasitic infections. Identifying sufficiently selective agonists or positive modulators of the TRPM5 channel has, to date, proved challenging which has limited its potential as a drug target.
In this publication, we focus on:
- the development of a high throughput screen using a fluorescent membrane potential assay for primary hit identification screening and selectivity assessment of TRPM5 channel positive modulators
- use of medium and high throughput electrophysiology assays (QPatch HTX and SyncroPatch 384PE) as follow-up screens to confirm activity and selectivity of identified hits
- the SyncroPatch 384PE assay for structure-activity relationship (SAR) expansion of the identified chemical series