Molecular Classification
Enzyme, Serine hydrolase, Alpha/beta fold hydrolase family
Other Names
Carboxylesterase, Carboxylesterase 1A1, CES1A1, hCE-1, B-esterase, Ali-esterase, Cocaine esterase, Procaine esterase, Carboxylesterase B, CAP-hydrolyzing enzyme, Carboxyesterase, Carboxylester lipase, Carboxylate esterase, Carboxylic ester hydrolase, Isocarboxazid amidase, Naproxen esterase, Non-specific carboxylesterase, Serine esterase 1 (SES1), Monocyte esterase, Cholesterol ester hydrolase (CEH)
Disease Roles
Cancer (deficiency may be associated with non-Hodgkin lymphoma or B-cell lymphocytic leukemia)Neurologic disease (related to detoxification and CNS protection)Pharmacogenetics of organophosphate poisoning (inhibition reduces monocyte anti-tumor activity)

Carboxylesterase 1 Overview

Carboxylesterase 1 (CES1) is a major human serine hydrolase enzyme belonging to the alpha/beta-hydrolase fold family. It is highly expressed in the liver, with additional distribution in the gastrointestinal tract, lung, and other tissues. CES1 catalyzes the hydrolysis of a wide variety of endogenous and exogenous esters, including drugs, prodrugs, environmental toxicants, and lipid molecules. It plays a critical role in phase I drug metabolism, activating certain prodrugs (such as oseltamivir and dabigatran), detoxifying xenobiotics, and regulating lipid and cholesterol homeostasis. CES1 activity shows substantial genetic and inter-individual variability, which can significantly influence therapeutic outcomes and toxicity of many drugs, especially those commonly prescribed or used as prodrugs. Carboxylesterase 1 is considered a clinically relevant therapeutic target, and its function or dysfunction is implicated in cancer, infections, chemical toxicity, and metabolic diseases.

Mechanism of Action

Hydrolysis (inactivation or activation of drugs through catalytic cleavage of ester/amide/thioester/carbamate linkages) Prodrug activation (conversion of prodrug to active metabolite) Detoxification (catalysis of xenobiotic metabolism for excretion)

Biological Functions

Drug metabolism (phase I metabolism)
Detoxification of xenobiotics and toxicants
Activation/inactivation of prodrugs and drugs
Hydrolysis of ester-, amide-, thioester-, and carbamate-bond-containing compounds
Lipid homeostasis (metabolism of cholesteryl esters, long-chain fatty acid esters, triacylglycerols, other endogenous lipids)
Regulation of cellular cholesterol esterification
Detoxification in the lung/central nervous system

Disease Associations

Cancer (deficiency may be associated with non-Hodgkin lymphoma or B-cell lymphocytic leukemia)
Neurologic disease (related to detoxification and CNS protection)
Pharmacogenetics of organophosphate poisoning (inhibition reduces monocyte anti-tumor activity)
Drug toxicity and efficacy (due to genetic polymorphisms and interaction with many drugs)
Other (pharmacogenetic disorders, infection/detoxification roles)

Safety Considerations

  • Pharmacogenetic variability (affecting drug efficacy and toxicity)
  • Organophosphate-induced inhibition (can cause immunosuppression and reduced detoxification)
  • Off-target prodrug/toxicant activation (unintended bioactivation or inactivation)

Interacting Drugs

Methylphenidate
Clopidogrel
Oseltamivir
Dabigatran
Irinotecan
Capecitabine
Sofosbuvir
Niraparib
Omidenepag isopropyl
Mirdametinib
Serdexmethylphenidate
Various ACE inhibitors
Cocaine
Heroin
Environmental toxicants (e.g., pyrethroids)

Associated Biomarkers

Biomarker
CES1 genetic variants (for drug response and pharmacogenetics)
CES1 expression/activity (prognostic for some drug responses, sensitivity to toxicants, and potentially in certain cancers)