Application Note: Utility Of Different Test Systems For Determining Carboxylesterase Substrate Specificity And Inhibition Potential
5 June 2014

This study evaluates a number of different enzyme systems for investigating hydrolysis of drug esters. A comparison of a panel of hCE1 and hCE2 substrates in human liver and intestinal microsomes highlighted the limitations in these systems in determining CES substrate specificity. In contrast recombinant CES enzymes proved more useful for this purpose. A comparison of recombinant enzymes from different suppliers was also evaluated. In addition to stability studies, enzyme kinetics were established in the recombinant systems using specific probe substrates (trandolapril for hCE1 and irinotecan for hCE2) to develop an assay suitable for the testing of compounds as potential CES inhibitors.