Scientists from Sanofi and Axxam have developed two novel high-throughput screening (HTS) assays for GLUT9/SLC2A9, a crucial urate transporter, advancing the field of drug discovery for hyperuricemia and gout treatment.

GLUT9 plays a vital role in urate homeostasis, being the sole transporter of reabsorbed urate from renal epithelial cells to blood. Elevated serum urate levels are associated with various disorders, including gout, hypertension, and cardiovascular diseases.

Existing methods for studying GLUT9 function and pharmacological inhibition, such as [14C]-labeled urate uptake assays or TEVC, are unsuitable for high-throughput drug discovery due to their low sample throughput.

The study introduces two complementary assay technologies tailored for HTS campaigns targeting GLUT9:

Membrane Potential Assay: This primary screening method utilizes the FLIPR® Membrane Potential Assay (FMP-Blue-Dye). It detects changes in cell membrane potential caused by ion transport through GLUT9.

Solid-Supported Membrane (SSM)-Based Electrophysiological Assay: This secondary screening method employs the Nanion SURFE2R technology. It characterizes electrogenic membrane proteins by measuring transient currents generated by substrate or ligand application.

The combination of these assays offers several advantages for drug discovery:

High-throughput capability: They enable rapid screening of large compound libraries, accelerating the drug discovery process.

Complementary approaches: The combination of a cell-based assay (membrane potential) and a cell-free assay (SSM-based electrophysiology) provides robust validation of potential hits.

Electrogenic transport detection: Both assays capitalize on GLUT9’s electrogenic nature, allowing for sensitive detection of transporter activity and inhibition.

Versatility: The SSM-based assay can be applied to purified proteins, proteoliposomes, or membrane vesicles, offering flexibility in sample preparation.

By developing these assays, the Sanofi and Axxam scientists have provided valuable tools for identifying novel, selective GLUT9 inhibitors, potentially leading to more effective treatments for hyperuricemia and gout.

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Find the full article here: The development of a novel high-throughput membrane potential assay and a solid-supported membrane (SSM)-based electrophysiological assay to study the pharmacological inhibition of GLUT9/SLC2A9 isoforms in a drug discovery program

Are you studying SLC transporters? Have you considered using SSM-based electrophysiology? Learn more about it here: https://www.nanion.de/products/surfe2r-n1/