SR 1555 is a novel RORγ-specific synthetic ligand.

In vitro: In a GAL4-NR chimeric co-transfection assay, SR1555 was devoid of LXR, FXR, and RORα activity, but it dose-dependently repressed the activity at RORγ (IC50: ≈ 1.5 μM). In competitive radioligand binding assays, SR1555 bound to RORγ (IC50: 1 μM). SR1555 specifically targeted RORγ and inhibited its transcriptional activity leading to suppression of IL-17 gene expression. EL4 cells treated SR1555 (10 μM) for 24 h inhibited Il17a gene expression by greater than 70%, demonstrating that SR1555 could inhibit the expression of this TH17 mediated cytokine. SR1555 not only inhibited TH17 cell development and function but also increased the frequency of T regulatory cells [1].