Kinetic assays to characterize fluorescent ligand binding to muscarinic acetylcholine M1 receptor

Understanding how ligands engage the muscarinic M1 receptor is key to advancing therapies for neurodegenerative disorders. In this study, we introduce complementary kinetic fluorescence approaches that enable real‑time monitoring of ligand binding at the M1 receptor with high sensitivity. Using the fluorescent tracer UR‑MK342, we not only obtain robust affinity estimates across a diverse panel of muscarinic ligands, but also uncover unexpected complexity in binding behaviour. Notably, the ability to follow allosteric modulators in live competition assays positions this platform as a powerful tool for exploring nuanced GPCR pharmacology.
Check out our paper here: https://doi.org/10.1016/j.bcp.2026.117911