Technology combination to address GPCR allosteric modulator drug-discovery pitfalls

Allosteric modulators (AMs) represent a novel paradigm to therapeutically target G-protein-coupled receptors (GPCRs). However, their identification and characterization using standard functional assays remain elusive due to the ‘context-dependent phenomena’. Novel technological approaches such as combining a Fluorescence Resonance Energy Transfer (FRET)-based library filtering with a Bioluminescence Resonance Energy Transfer (BRET)-based multiparametric compound profiling can circumvent the limitations of current GPCR screening processes and simplify the discovery of biased AMs.