Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Ioannis Mouratidis Supervisor: Doc. PharmDr. Petr Pávek Ph.D. Testing of newly synthesized compounds with constitutive androstane receptor (CAR) Interactions of a diverse array of nuclear receptors with numerous isolated compounds (ligands) have been extensively investigated during the last years. The reason of this intense research activity is, of course, the wide therapeutic potential of the nuclear receptors super- family. It is known that they interact with the metabolism and excretion of various compounds, endogenous or exogenous that interfere with the homeostasic mechanisms of the living organisms. In my study, I tested the activation of a specific orphan nuclear receptor known as constitutive androstane receptor (CAR). I tested 11 structurally different compounds as well as a known inhibitor of CAR (clotrimazole) and an activator (CITCO). To test these interactions between these compounds and CAR, I used the method of the mammalian two- hybrid system, a method where ligand-protein interactions are studied in an environment close to that in vivo. The method is based on the Dual-Luciferase Reporter kit, which made the quantification of the CAR responsive luciferase reporter...

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