Discovery and characterization of small-molecule TGR5 ligands with agonistic activity
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- dc.contributor.author Papadopoulos, Maria Giovanna Eva
- dc.contributor.author Perhal, Alexander F.
- dc.contributor.author Medel Lacruz, Brian
- dc.contributor.author Ladurner, Angela
- dc.contributor.author Selent, Jana
- dc.contributor.author Dirsch, Verena M.
- dc.contributor.author Kolb, Peter
- dc.date.accessioned 2025-05-19T06:16:08Z
- dc.date.available 2025-05-19T06:16:08Z
- dc.date.issued 2024
- dc.description.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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Papadopoulos MGE, Perhal AF, Medel-Lacruz B, Ladurner A, Selent J, Dirsch VM, et al. Discovery and characterization of small-molecule TGR5 ligands with agonistic activity. Eur J Med Chem. 2024 Oct 5;276:116616. DOI: 10.1016/j.ejmech.2024.116616
- dc.identifier.doi http://dx.doi.org/10.1016/j.ejmech.2024.116616
- dc.identifier.issn 0223-5234
- dc.identifier.uri http://hdl.handle.net/10230/70429
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Eur J Med Chem. 2024 Oct 5;276:116616
- dc.rights © 2024 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
- dc.subject.keyword CRE-Luciferase assay
- dc.subject.keyword Molecular docking
- dc.subject.keyword Molecular dynamics simulations
- dc.subject.keyword PAM
- dc.subject.keyword Structure-based drug design
- dc.subject.keyword TGR5
- dc.title Discovery and characterization of small-molecule TGR5 ligands with agonistic activity
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion