Figure 1: Identification of ivermectin as a novel FXR ligand.
From: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism
(a) Various coregulator binding motifs bind to FXR in response to 0.5 μM ivermectin or GW4064 by AlphaScreen assay. The peptide sequences are listed in Methods. (b) Receptor-specific transactivation by ivermectin. COS-7 cells were cotransfected with plasmids encoding full-length nuclear receptors and their cognate response reporters, respectively (see Methods). After transfection, cells were treated with dimethyl sulphoxide (DMSO), 0.5 μM ivermectin or ligands specific for each receptor: FXR, 0.5 μM GW4064; peroxisome proliferator-activated receptor (PPAR)α, 1 μM GW590735; PPARδ, 1 μM GW0472; PPARγ, 1 μM rosiglitazone; GR, 0.1 μM dexamethasone; progesterone receptor (PR), 0.1 μM progesterone; RARα and RARβ, 1 μM all-trans-retinoic acid; PXR, 10 μM rifampicin; constitutive androstane receptor (CAR), 5 μM CITCO. (c) Dose responses of ivermectin in transactivating FXR. COS-7 cells were cotransfected with full-length FXRα and an EcRE luciferase reporter. After transfection for 5 h, cells were treated with various concentrations of ivermectin or GW4064. For b and c, luciferase data were normalized to renilla activity cotransfected as an internal control. Values are the means±s.e.m. of three independent experiments.
