SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR)α/γ.

SR1078 is a synthetic RORα/RORγ ligand that modulates the conformation of RORγ in biochemical assays and activates RORα and RORγ-driven transcription. It stimulates the expression of endogenous ROR target genes in HepG2 cells expressing both RORα and RORγ. In a cell-based chimeric receptor Gal4 DNA-binding domain-NR ligand-binding domain cotransfection assay, SR1078 significantly inhibits the constitutive transactivation activity of RORα and RORγ, without affecting FXR, LXRα, or LXRβ. Treatment of cells with SR1078 (10 μM) in a RORα cotransfection assay significantly increases transcription, and similarly, in a RORγ cotransfection assay, SR1078 stimulates RORγ-dependent transcription activity[1].

The pharmacokinetics of SR1078 were evaluated in mice, revealing notable exposure. Plasma concentrations reached 3.6 μM one hour post 10 mg/kg i.p. injection and remained above 800 nM at 8 hours. These levels are adequate for proof-of-principle experiments assessing ROR target gene expression. Mice treated with SR1078 (10 mg/kg i.p.) showed significant stimulation of both G6Pase and FGF21 gene expression in liver mRNA, compared to vehicle control [1].