{Reference Type}: Journal Article
{Title}: Discovery and characterization of small-molecule TGR5 ligands with agonistic activity.
{Author}: Papadopoulos MGE;Perhal AF;Medel-Lacruz B;Ladurner A;Selent J;Dirsch VM;Kolb P;
{Journal}: Eur J Med Chem
{Volume}: 276
{Issue}: 0
{Year}: 2024 Oct 5
{Factor}: 7.088
{DOI}: 10.1016/j.ejmech.2024.116616
{Abstract}: The Takeda G protein-coupled receptor 5 (TGR5) is activated endogenously by primary and secondary bile acids. This receptor is considered a candidate target for addressing inflammatory and metabolic disorders. We have targeted TGR5 with structure-based methods for ligand finding using the recently solved experimental structures, as well as structures obtained from molecular dynamics simulations. Through addressing the orthosteric as well as a putative allosteric site, we identified agonists and positive allosteric modulators. While the predicted binding locations were not in line with their efficacy, our work contributes activating small-molecule ligands that we have thoroughly characterized in vitro.