Supplementary Material for: In vitro and in vivo Characterization of a New Organic Nitrate Hybrid Drug Covalently Bound to Pioglitazone

Background/Aims: Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. Methods: In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. Results: In vitro, CLC-3000 displayed more potent vasodilation than pioglitazone alone or classical nitrates. In vitro, some e…