GLUT modulator screening assay for glucose uptake and bioenergetic profiling

Overview

This offering provides a versatile screening assay designed to identify and characterise modulators of glucose transporter (GLUT) activity across a wide range of cell types. By combining measurements of glucose uptake and lactate secretion with bioenergetic profiling, the assay delivers a comprehensive picture of how candidate compounds influence cellular energy metabolism. The platform is particularly relevant for discovering inhibitors of glucose uptake, with potential applications in diabetes, cancer, immune-related conditions, and nutrition science. Its kinetic, multiplexed design enables researchers to link exposure-response relationships to pharmacokinetic parameters, supporting informed decision-making in early-stage development.

Technical specifications

• Kinetic glucose uptake measurement using 2-deoxyglucose as a surrogate for endogenous glucose, with commercially available reagents
• Lactate secretion profiling to assess downstream metabolic consequences of GLUT modulation
• Bioenergetic assessment via the Agilent Seahorse XF Mito Stress Test, measuring ATP production rates and mitochondrial function in THP-1 cells and other relevant cell models
• Multiplexed viability assessment to distinguish true GLUT-mediated effects from cytotoxicity
• Gene expression analysis of SLC transporter family members using qPCR TaqMan assays to identify compensatory mechanisms
• In silico binding analysis to predict interactions between candidate molecules and GLUT transporters such as SLC2A1
• Cell-type agnostic design adaptable to any target cell, with demonstrated results showing up to 90% reduction in glucose accumulation with efavirenz and 70% with lopinavir in THP-1 cells
• Improved throughput format suitable for screening active and non-active ingredients at physiologically relevant concentrations with EC50 determination

Technology readiness level

The assay has been validated through published research demonstrating its ability to assess the impact of antiretrovirals on glucose uptake, compensatory GLUT expression, and bioenergetic profiles. Future work will deploy the assay in an improved throughput format to screen molecules for GLUT modulation, with parallel viability and ATP rate measurements, and lactate secretion analysis. This next phase is estimated to take approximately six months and aims to establish EC50 values linked to pharmacokinetic parameters. The platform is ready for collaborative application with partners seeking to evaluate compound libraries for metabolic and immunological applications.