2. Academic Validation
  3. Development of a BRET based chloride biosensor for high throughput screening of KCC2 modulators

Development of a BRET based chloride biosensor for high throughput screening of KCC2 modulators

  • SLAS Discov. 2025 Jun 24:35:100245. doi: 10.1016/j.slasd.2025.100245.
Charles S Lay 1,  Elvira Diamantopoulou 2,  Katharina L Dürr 2,  Idlir Liko 2,  Steven J Charlton 2
Affiliations

Affiliations

  • 1 OMass Therapeutics, Building 4000, John Smith Dr, ARC, Oxford, OX4 2GX, UK. Electronic address: charlie.lay@omass.com.
  • 2 OMass Therapeutics, Building 4000, John Smith Dr, ARC, Oxford, OX4 2GX, UK.
PMID: 40570963 DOI: 10.1016/j.slasd.2025.100245
Abstract

The generation of action potentials in neuronal cells and many Other physiological processes involve the transport of chloride ions. Whilst there have been advances in chloride imaging techniques utilizing FRET biosensors, there is a lack of methodologies that are amenable to high-throughput screening for drug discovery. In this study, we developed a novel BRET-based biosensor (Glorider), utilizing a chloride-sensitive GFP variant fused to NanoLuciferase. The Glorider biosensor was then used to kinetically measure the effect of WNK, KCC2 and NKCC1 modulators in real time in living cells, including recently reported KCC2 agonists.

Keywords

Biosensors; Chloride; Chloride-imaging; Drug-discovery; KCC2; Rett-syndrome; Screening; Solute-carriers.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100626
    99.75%, WNK Inhibitor