ArticleRSC medicinal chemistry2026
Oleanolic acid-derived triterpenoids with dual TGR5 agonistic and RORγ inverse agonistic activity.
Article in RSC medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Takeda G protein-coupled receptor 5 (TGR5) and the retinoid-related orphan receptor γ (RORγ) are key regulators of metabolic and immune pathways. This makes them attractive targets for developing anti-inflammatory and metabolic therapeutics. In this study, we designed and synthesised a series of oleanolic acid-derived triterpenoid derivatives to explore their potential as dual modulators of these receptors. The focus of the structural modifications was on the double bond, C-3 substitution, and A-ring rearrangements in order to investigate their impact on biological activity and establish structure-activity relationships within the pentacyclic triterpene scaffold. Biological evaluation using CRE-luciferase reporter assays identified oleanolic acid (1), oleanonic acid (5), and compounds 7 and 8 as TGR5 agonists with concentration-dependent activities. Oleanolic acid (1) and the newly identified seco-derivative 8 displayed the most favourable potency and efficacy profiles. Gal4-RORγ reporter assays demonstrated inverse agonistic activity for oleanolic acid (1) and compounds 7 and 8. Although 7 and 8 exhibited lower potency than 1, both retained pronounced inhibitory efficacy, indicating that substantial scaffold rearrangement remains compatible with RORγ modulation. A resazurin conversion assay showed no evidence of cytotoxicity under the conditions tested, supporting that the observed receptor effects were not attributable to general cytotoxicity. Molecular modelling and Nwat-MMGBSA calculations supported the experimental findings and emphasized the role of conserved buried water molecules in stabilising ligand-receptor interactions in both targets. Overall, these findings identify oleanolic acid-derived triterpenoids as promising scaffolds for dual TGR5/RORγ modulation and provide valuable insights for the future development of multitarget-directed ligands targeting inflammatory and metabolic disorders.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.