Following a screen of known nuclear receptor ligands against the entire nuclear receptor superfamily, the liver X receptor (LXR) agonist T0901317 was identified as a retinoic acid receptor-related orphan receptor (ROR) ligand. T0901317 has substantial promiscuity against other nuclear receptors. Various alterations in the structure led to the discovery of an agonist of RORα and RORγ (SR1078), an inverse agonist of RORα and RORγ (SR1001), and a RORγ-selective inverse agonist (SR2211). FXR, farnesoid X receptor; PXR, pregnane X receptor.