Carboxylesterase (CE) inhibition assay

Understand if your compound is an inhibitor of carboxylesterases.

Carboxylesterase (CE) inhibition is a non-CYP mediated metabolism assay within our portfolio of in vitro ADME screening services. Cyprotex deliver consistent, high quality data with the flexibility to adapt protocols based on specific customer requirements.

Determining potential inhibition of carboxylesterase enzymes

Human carboxylesterases (CE) are Phase I drug metabolizing enzymes of the serine hydrolase superfamily. They hydrolyze a variety of ester containing drugs and prodrugs.
Carboxylesterase inhibitors may play a role in improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these enzymes.
Cyprotex’s carboxylesterase inhibition assay identifies if your compound is an inhibitor of the carboxylesterase (CE) isoform, hCE1, using hCE1-b and hCE1-c recombinant enzymes.

CE inhibitors potentially have dual roles in modulating drug action, by both reducing induced toxicity and/or increasing molecule half-life.

¹Hatfield M.J. and Potter P.M. (2011) Expert Opin Ther Pat 21(8); 1159-1171

Protocol

Carboxylesterase inhibition assay protocol

Test System	hCE1-b and/or hCE1-c expressed enzymes
Substrates	Trandolapril (hCE1)
Metabolites	Trandolaprilat (hCE1)
Test Article Concentrations	0, 0.4, 1, 4, 10, 40 and 100 µM (different concentrations available)
Positive Control Inhibitors	Benzil (hCE1)
Test Article Requirements	100 µL of a 40 mM DMSO solution (or equivalent amount in solid)
Analysis Method	LC-MS/MS
Data Delivery	IC₅₀ Standard error of IC₅₀ % Control at each concentration