Examination of Potential Ligands of the Constitutive Androstane Receptor CAR

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Vojtěch Zadák Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of rigorous thesis: Examination of potential ligands of the constitutive androstane receptor CAR Year of completion: 2010 The constitutive androstane receptor - CAR is a representative of nuclear receptors that form a super-family of ligand-activated transcription factors regulating expression of target genes. In the last decade, CAR was mainly investigated in connection with an induction of biotransformation enzymes by remedies or other xenobiotics but in the past few years the research has also concentrated on a role of this receptor in hormone, lipid and energy homeostasis. Recently, there have been revealed some new important metabolic functions of CAR that may establish this "xenobiotic receptor" as a new therapeutic target for treatment of type 2 diabetes, obesity and dyslipidemia. The aim of this experimental rigorous thesis has been the examination of potential ligands of the human CAR (hCAR) from a given group of 16 chemicals with a defined structure. Using methods gene reporter assay, two-hybrid assay and one-hybrid assay we have tested this group from the perspective of an interaction with hCAR. The..