Understand if your compound is a substrate of carboxylesterases.
Carboxylesterase (CE) reaction phenotyping 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.
Of the enzymes involved in phase I reactions, cytochrome P450 enzymes play a pivotal role in drug metabolism (i.e. approximately 75% of clinically used drugs), followed by esterases, which contribute to the metabolism of 10% of the clinical, therapeutic drugs that contain ester, amide and thioester bonds.
1Fukami T. and Yokoi T. (2012), Drug Metab Pharmacokinet 27(5); 466-477
|Test Systems*||hCE1-b, hCE1-c, hCE2 expressed enzymes, or
Human liver/intestinal microsomes incubated with and without CE inhibitor
|Test Article Concentration||1 µM|
|Positive Control Substrates||Trandolapril (hCE1 substrate)
Irinotecan (hCE2 substrate, monitoring for formation of 7-ethyl-10-hydroxycamptothecin)
|Test Article Requirements||100 µL of a 10 mM DMSO solution (or equivalent amount in solid)|
|Data Delivery||Parent compound remaining at each time point for each isoform
Standard error of half life
*Alternative species or enzyme sources (i.e. plasma, blood) are available on request. We also have experience in evaluating other esterase mediated metabolism such as paraoxonase and butyrylcholinesterase metabolism.
1 Fukami T and Yokoi T. (2012) The emerging roles of human esterases. Drug Metab Pharmacokinet 27(5); 466-477
2 Imai T. (2006) Human carboxylesterase isozymes: catalytic properties and rational drug design. Drug Metab Pharmacokinet 21(3); 173-185