Structures of ligands that interact with FXR and/or PXR. Compounds that are agonists for FXR or PXR are shown in panels (A) and (B), respectively. The effective agonist concentration that elicits 50% of maximum activation of the respective human receptor (EC50) is provided, with the exception of PCN, a selective mouse PXR ligand, where the EC50 for mouse PXR is shown. Guggulsterone, a promiscuous nuclear receptor ligand that acts as both an FXR antagonist and a PXR agonist, is shown in (C). Ursodeoxycholic acid, a naturally occurring epimer of chenodeoxycholic acid that is used in the therapy of some cholestatic liver disorders, but is not thought to significantly interact with nuclear receptors, is shown for comparative purposes in (D). CDCA, chenodeoxycholic acid; PCN, pregnenolone 16α-carbonitrile.