Consensus ligand- and structure-based virtual screening uncovers chemically diverse GLP-1 receptor agonists, including a small peptide with dual GIPR activity
- The pipeline combines ligand-based descriptors, multi-fingerprint and electrostatic similarity, pharmacophore models and docking to several receptor conformations, with a consensus rule to pick compounds.
- It targets the flexible class B1 GLP-1 receptor, where single-method screens tend to be biased and recover few chemotypes.
- Selected hits were tested in cells, then probed by binding-site mutagenesis and competition binding.
- Three structurally distinct agonists emerged, one non-peptide and two peptides; a pentapeptide acted as a full agonist, also hit GIPR, but with modest potency.
💡 Points Based on the abstract
Three hits is a result, but the missing number is hit rate against how many compounds were tested, and against a plain docking-only or similarity-only baseline. Without that, consensus value is unproven. For a team: check whether the pentapeptide's activity is real receptor pharmacology, and whether modest potency leaves room for optimisation.