Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ).

ABSTRACT: Targeting retinoic acid-related orphan receptor γ (RORγ) with inverse agonists presents a promising therapeutic strategy for treating autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis. Through structure-based virtual screening, we identified a lupane-type pentacyclic triterpenoid, (2Z)-2-(2-furanylmethylene)-3-oxolup-20(29)-en-28-oic acid (15), as a new inverse agonist of RORγ. The compound exhibited IC₅₀ values of 0.4 μM and 0.9 μM in Gal4-RORγ and full-length RORγ luciferase assays, respectively. Compound 15 showed improved potency and efficacy compared to a structurally related known inverse agonist, betulinic acid. Among the four additional analogues tested (15.1-15.4), two (15.2 and 15.3) also de

SUBMITTER: Schwarz PF 

PROVIDER: S-EPMC12379159 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature