Author/Editor		Režen, Tadeja; Hafner, Mateja; Kortagere, Sandhya; Ekins, Sean; Hodnik, Vesna; Rozman, Damjana
Title		Rosuvastatin and atorvastatin are ligands of the human CAR/RXR[alpha] complex
Type		članek
Publication year		2017
Volume		str. str.
ISSN		0090-9556 - Drug metabolism and disposition: the biological fate of chemicals
Language		eng
Abstract		Statins are well known lipid lowering agents that inhibit the enzyme HMG-CoA reductase. They also activate drug metabolism but their exact receptor-mediated action has not been proven so far. The aim of this study was to test if atorvastatin and rosuvastatin are direct ligands of human CAR. We measured binding activities of atorvastatin and rosuvastatin to the human CAR/RXR[alpha]-LBD heterodimer with surface plasmon resonance (SPR). Additionally, three-dimensional models of CAR/RXR[alpha]-LBD were constructed by ligand-based and structure-based in silico modelling. Experiments and computational modeling show that atorvastatin and rosuvastatin bind to the human CAR/RXR[alpha]-LBD heterodimer, suggesting both can modulate the activity of CAR through direct interaction with the LBD of this receptor. In conclusion, we confirm that atorvastatin and rosuvastatin are direct ligands of CAR. The clinical consequences of CAR activation by statins are in their potential drug-drug interactions, and changes in glucose and energy metabolism.
Keywords		statins lipids atorvastatin rosuvastatin statini lipidi atorvastatin rosuvastatin