Abstract 1167 Development of a fluorogenic chemical tool to study human carboxylesterase 2 in live cells

Carboxylesterases are enzymes that play a role in the hydrolysis of esters to carboxylic acid and alcohol.Human carboxylesterases (CESs) are involved in the metabolism of pharmaceuticals that contain a wide range of esters.CES activity is known to vary among individuals due to genetic and environmental factors.This interindividual variability in CES activity has been demonstrated to cause varying outcomes when patients are treated with drugs metabolized by CESs.A variety of well-characterized fluorogenic chemical tools have been developed to study one of the two major forms of CESs, carboxylesterase 2 (CES2).These tools, however, have not achieved widespread use.We hypothesize that this is due to the difficulty in obtaining these CES2 fluorogenic chemical tools.Here, we seek to characterize a commercially available compound, Fluorescein Diacetate (FDA), as a chemical tool for use in live cells to study CES2.To characterize FDA, we carried out a variety of in vitro stability studies before deploying FDA in live cells to determine if it can be used to study CES2 activity using fluorescence microscopy.Overall, our studies seek to expand the availability and accessibility of chemical tools and methods to study CES2 which we believe will lead to better clinical outcomes for patients.