Human CES2 (Cocaine esterase) ELISA Kit

Lung cancer has been widely considered to be one of the most common and severe types of cancers, and irinotecan is the common drug clinically used to treat lung cancer. Irinotecan undergoes two-step metabolic reaction, including carboxylesterase 2 (CES2)-catalyzed hydrolysis metabolism and UDPglucuronosyltransferase (UGT) 1A1 and 1A7-catalyzed glucuronidation reaction. This study aims to investigate the inhibition of praeruptorin compounds towards drug-metabolizing enzymes (DMEs) involved in the metabolism of irinotecan, including CES2, UGT1A1, and UGT1A7. In vitro human liver microsomes (HLMs)-catalyzed hydrolysis metabolism of fluorescein diacetate (FD) was used to investigate the inhibition of praeruptorin compounds on CES2, and in vitro recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was used to determine the inhibition of praeruptorin compounds on the activity of UGT1A1 and UGT1A7. 100 mu M of praeruptorin compounds were selected to determine the inhibition on the activity of CES2, UGT1A1, and UGT1A7. 100 mu M of praeruptorin C, D, and E inhibited approximately 60% activity of CES2 (p <.01). 100 mu M of praeruptorin C, D, and E showed negligible inhibition on the activity of UGT1A1. For UGT1A7, praeruptorin C showed strong inhibition potential on the activity of UGT1A7 (p < 0.01), but praeruptorin D and E did not show significant inhibition on the activity of UGT1A7. In conclusion, praeruptorin C, D, and E can alter the metabolic behavior of irinotecan through affecting the activity of CES2 or UGT1A7.

Both aspirin and vicagrel are effective antiplatelet drugs, with the potential for concomitant use as another dual-antiplatelet therapy for the prevention of recurrent thrombotic or ischemic events. Because they both are the substrates of carboxylesterase 2 (CES2), aspirin attenuated the metabolic activation of and platelet response to vicagrel in mice treated with the two drugs concomitantly. In this study, we sought to clarify whether vicagrel could affect platelet responses to aspirin and their underlying mechanisms. Plasma levels of aspirin and salicylic acid were determined by liquid chromatography-tandem mass spectrometry, inhibition of arachidonic acid (AA)-induced whole-blood platelet aggregation by aspirin was assessed with an aggregometer, and their antithrombotic effects were evaluated by arteriovenous shunt thrombosis model. The results showed that concomitant use of vicagrel (5, 10, or 20 mg/kg) led to an average of 55% and 77% increases in systemic exposure of aspirin (C(max)( )and AUC(0-t)) and 2.8-fold increase in suppression of AA-induced platelet aggregation in mice when compared with use of aspirin alone. In the rat thrombus formation model, vicagrel (1 mg/kg) enhanced inhibition of thrombosis formation by aspirin (5 mg/kg), but not vice versa. We conclude that vicagrel increases platelet responses to aspirin and also enhances inhibition of thrombus formation of aspirin due to decreased CES2-catalyzed aspirin inactivation in rodents, and that an integrated net effect on thrombus formation in vivo is superior to inhibition of AA- or ADP-induced platelet aggregation ex vivo by either of the two drugs if taken concomitantly.