Affinage

CES1

Liver carboxylesterase 1 · UniProt P23141

Round 2 corrected
Length
567 aa
Mass
62.5 kDa
Annotated
2026-04-28
130 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Insufficient on-target evidence to synthesize a narrative — discovery timeline does not match the canonical CES1 protein.

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CES1 (carboxylesterase 1) is expressed as a serine esterase in human alveolar macrophages and monocytes, where it is released into bronchoalveolar lavage fluid associated with surfactant; it is virtually identical to liver microsomal carboxylesterase, establishing CES1 as both a hepatic and macrophage enzyme with detoxification function. Protein purification, [3H]DFP labeling, NH2-terminal sequencing, PCR cloning from macrophage cDNA library, Northern blot The Journal of biological chemistry High 1918003
1993 CES1 (hCE) encodes a 568-amino-acid serine hydrolase with an 18-aa signal peptide; baculovirus-expressed hCE hydrolyzes aromatic and aliphatic esters but not amides or fatty acyl-CoA esters; N-glycosylation is essential for maximal catalytic activity, as tunicamycin inhibition substantially reduces activity; two highly similar variants (hCE and hCEv) were identified as distinct gene family members. cDNA cloning, baculovirus expression in Sf9 cells, enzymatic assays, tunicamycin inhibition, somatic cell hybrid chromosome mapping Biochemistry High 8218228
1997 Purified human liver CES1 (hCE-1) catalyzes hydrolysis of cocaine to benzoylecgonine, deacetylation of heroin to 6-acetylmorphine, and ethanol-dependent transesterification of cocaine to cocaethylene; binding is stereoselective for (R)-(-)-cocaine, and the methyl ester, benzoyl, and N-methyl groups of cocaine are critical for binding affinity. Purified enzyme kinetic assays, competitive inhibition with 4-methylumbelliferyl acetate, stereoisomer comparison Drug metabolism and disposition High 9311626
2000 CES1 expressed in human macrophages functions as a cholesteryl ester hydrolase (CEH); overexpression in COS cells yielded >20-fold increased CEH activity; overexpression in CHO-K1 cells impaired LDL receptor mRNA upregulation under cholesterol-deficient conditions, placing CES1 in the intracellular cholesteryl ester metabolism pathway. RT-PCR, cDNA cloning, transient transfection in COS-1/COS-7/CHO-K1 cells, enzymatic activity assay, Northern blot Physiological genomics High 11015575
2003 Crystal structures of human CES1 (hCE1) in complex with the cocaine analog homatropine and heroin analog naloxone reveal that the active site contains both a specific and a promiscuous compartment enabling metabolism of structurally distinct chemicals; a separate surface ligand-binding site regulates the trimer-hexamer equilibrium and allows each monomer to bind two narcotic molecules simultaneously. X-ray crystallography of hCE1 glycoprotein complexes Nature structural biology High 12679808
2003 Crystal structure of hCE1 with tacrine (2.4 Å) shows tacrine binds in multiple orientations within the catalytic gorge, in contrast to acetylcholinesterase; this promiscuity is structurally explained by the larger, flexible active-site architecture of hCE1; tacrine derivatives were identified as low-micromolar CES1 inhibitors. X-ray crystallography, inhibitor screening assays Chemistry & biology High 12725862
2004 CES1A1 (along with CES2 and CES3) hydrolyzes irinotecan and its oxidative metabolites NPC and APC to the active metabolite SN-38; the relative catalytic efficiency for CPT-11 hydrolysis is CES2 > CES1A1 >> CES3. Purified recombinant enzyme kinetic assays Drug metabolism and disposition High 15100172
2006 Crystal structures of hCE1 with CoA, palmitate, cholate, and taurocholate reveal three ligand-binding sites (active site plus two additional sites), all exhibiting non-specific binding; this multisite promiscuity structurally explains CES1's ability to perform cholesterol ester hydrolysis, fatty acyl-CoA hydrolysis, acyl-CoA:cholesterol acyltransfer, and fatty acyl ethyl ester synthesis depending on cellular context. X-ray crystallography of four hCE1 complexes with endogenous substrates/analogs Journal of molecular biology High 16962139
2008 Two CES1 coding mutations, p.Gly143Glu (exon 4) and p.Asp260fs (exon 6 frameshift/premature stop), cause complete loss of hydrolytic activity toward methylphenidate; p.Gly143Glu retains only 21.4% catalytic efficiency (Vmax/Km) and p.Asp260fs retains 0.6% relative to wild-type using p-nitrophenyl acetate; minor allele frequency of p.Gly143Glu is 3.7%/4.3%/2.0%/0% in white/black/Hispanic/Asian populations. DNA sequencing, in vitro functional expression, kinetic assays with methylphenidate and p-nitrophenyl acetate American journal of human genetics High 18485328
2008 Human CES1 (HCE1) is expressed predominantly in liver and shows age-dependent ontogeny: fetal liver has lowest expression (~10-fold lower than adult), child liver is intermediate; CES1 selectively hydrolyzes oseltamivir over CES2, and adult microsomes are ~4× more active than child and ~10× more active than fetal microsomes; large inter-individual variability (up to 100-fold in protein) exists within the same age group. RT-qPCR, Western immunoblotting across 104 liver samples (fetal, child, adult), hydrolytic activity assays Biochemical pharmacology High 18983829
2009 Mouse esterase-x/Ces1 (Es-x/Ces1), stably expressed in McArdle-RH7777 hepatocytes, reduces triacylglycerol (TG) accumulation by redirecting exogenous fatty acids toward beta-oxidation rather than TG synthesis, as evidenced by increased acid-soluble metabolites; this TG-lowering effect persisted with esterase inhibitor E600, indicating the mechanism is primarily reduction of fatty acid partitioning into TG rather than increased TG turnover; Es-x expression did not alter VLDL-TG or apolipoprotein B secretion. Stable transfection of McArdle-RH7777 cells, TG quantification, acid-soluble metabolite measurement, E600 inhibitor experiment, glycerol supplementation Biochimica et biophysica acta High 19651238
2012 CES1 is the primary enzyme responsible for hydrolytic inactivation of clopidogrel and its intermediate 2-oxo-clopidogrel in human liver S9 fractions; inhibition of CES1 by bis(4-nitrophenyl) phosphate significantly increased concentrations of clopidogrel active metabolite; CES1 variants G143E and D260fs have completely impaired catalytic activity toward clopidogrel and 2-oxo-clopidogrel, whereas variants G18V, S82L, and A269S show no significant effect. Human liver S9 fraction incubations, CES1 inhibitor experiments, transfected cell line S9 fractions, LC-MS/MS metabolite quantification The Journal of pharmacology and experimental therapeutics High 23275066
2013 The CES1 G143E variant carriers show significantly increased clopidogrel active metabolite levels and better clopidogrel response (reduced ADP-stimulated platelet aggregation) compared with non-carriers, confirming that CES1-mediated hydrolysis constitutes the primary inactivation route of clopidogrel in vivo. Clinical pharmacogenomics study (PAPI study, n=566 + 350 CHD patients), active metabolite measurement, platelet aggregation assay Pharmacogenetics and genomics High 23111421
2013 Recombinant human CES1 efficiently hydrolyzes enalapril, ramipril, and trandolapril (but not CES2), establishing CES1 as the primary activating enzyme for these ACE inhibitor prodrugs; enalapril shows substrate inhibition kinetics while ramipril and trandolapril follow Michaelis-Menten kinetics; isradipine and tacrolimus are identified as novel CES1 inhibitors. Recombinant enzyme assays, Michaelis-Menten/substrate inhibition kinetic modeling, inhibitor screening with human liver microsomes Drug metabolism and disposition High 24141856
2015 CES1 selectively activates ACE inhibitor prodrugs enalapril, ramipril, perindopril, moexipril, and fosinopril in human liver (not intestine or kidney); the G143E variant is a loss-of-function variant reducing enalapril activation to ~one-third of wild-type in human liver samples carrying the 143G/E genotype; neither CES1/CES1VAR nor CES1P1/CES1P1VAR genotypes/diplotypes affected hepatic CES1 expression or activity in normal liver samples. Human liver/intestine/kidney S9 fraction incubations, CES1 inhibitor (BNPP), recombinant transfected cell lines, 102 normal human liver samples The pharmacogenomics journal High 26076923
2015 Fluoxetine decreases CES1 expression and hydrolytic activity in HepG2 cells by decreasing pregnane X receptor (PXR) expression and increasing DEC1; PXR overexpression attenuated and PXR knockdown abolished CES1 decreases; DEC1 knockdown increased PXR and restored CES1, establishing a FLX→DEC1↑/PXR↓→CES1↓ transcriptional regulatory axis. HepG2 cell transfection (overexpression and siRNA knockdown), RT-PCR, Western blot, enzymatic activity assay Xenobiotica High 26340669
2016 Sacubitril is selectively activated (hydrolyzed) by CES1 in human liver S9 fractions but not by CES2 or in intestine/kidney/plasma; the G143E variant is a loss-of-function variant for sacubitril activation; human livers with G143E genotype show significantly impaired sacubitril activation. Incubation with human tissue S9 fractions, CES1-selective inhibitor BNPP, recombinant CES1 and CES2, transfected cell lines, human liver samples with G143E genotyping Drug metabolism and disposition High 26817948
2016 The CES1VAR genomic translocation (replacing 5'UTR, exon 1, and part of intron 1 with CES1P1 pseudogene sequence, minor allele frequency 17%) reduces CES1 mRNA by ~2.6-fold and allelic mRNA by ~1.35-fold; however, CES1VAR did not detectably alter CES1 protein expression or metabolizing activity toward enalapril, clopidogrel, or methylphenidate in liver. Sanger and Ion Torrent sequencing, allelic mRNA analysis (SNaPshot), quantitative targeted proteomics, luciferase reporter assays in HepG2 Pharmacogenetics and genomics High 26871237
2016 CES1 and CES2 protein abundance in human liver microsomes increases approximately 5-fold and 3-fold from neonates to adults, respectively; oseltamivir carboxylase activity correlates with CES1 protein abundance across pediatric and adult liver microsomes, validating the ontogeny function for PBPK modeling. LC-MS/MS proteomics with purified protein standards as calibrators and heavy-labeled peptide internal standards in 171 liver samples Drug metabolism and disposition High 27895113
2018 The CES1 G143E variant (p.Gly143Glu) reduces lipolytic activity to ~20% of wild-type; humanized mice expressing CES1G143E on a Ces1-null background fed a high-fat diet show reduced liver and plasma triacylglycerol levels; the hypolipidemic mechanism involves decreased VLDL secretion, decreased hepatic lipogenic gene expression, and increased fatty acid oxidation (elevated plasma ketone bodies and hepatic mitochondrial electron transport chain protein abundance). Humanized mouse model (liver-specific CES1WT, CES1G143E, CES1S221A expression on Ces1-/- background), high-fat diet feeding, TG/cholesterol measurements, lipogenic gene expression, ketone body assay, mitochondrial protein quantification Biochimica et biophysica acta. Molecular and cell biology of lipids High 29631096
2017 Global inactivation of Ces1/Ces1g in Ldlr-/- mice protects against atherosclerosis by inhibiting intestinal cholesterol and fat absorption (including reduced Niemann-Pick C1-like 1 expression), increasing macrophage cholesterol efflux (via ABCA1 and ABCG1 induction), promoting M2 macrophage polarization, and inducing hepatic cholesterol 7α-hydroxylase and sterol 12α-hydroxylase; paradoxically, hepatic-specific Ces1/Ces1g knockdown in Apoe-/- mice exacerbated atherogenesis. Ces1g-/- Ldlr-/- double knockout mice, Western diet feeding, atherosclerotic lesion quantification, intestinal cholesterol absorption assay, macrophage cholesterol efflux assay, gene expression analysis Scientific reports High 29259301
2019 Vitamin E reverses NAFLD-associated lipid accumulation in fructose-treated mice via upregulation of Nrf2 and CES1; the Nrf2 inhibitor ML385 abolished the protective effects of vitamin E on lipid metabolism, establishing a Nrf2→CES1 signaling axis in hepatic lipid homeostasis. NAFLD mouse model (fructose feeding), vitamin E treatment, Nrf2 inhibitor (ML385), histopathology, lipid assays, in vitro L02 cell experiments Digestive diseases and sciences Medium 31076985
2019 CES1 is the most abundant drug-metabolizing enzyme in human liver (~1% of entire liver proteome), responsible for 80-95% of total hepatic hydrolytic activity; alcohol is identified as a potent CES1 inhibitor that can alter therapeutic outcomes of CES1 substrate medications. Proteomic quantification studies (reviewed), inhibitor characterization studies (reviewed) Drug metabolism and disposition Medium 31871135
2020 CES1 in human monocytic THP-1 cells hydrolyzes prostaglandin D2-glyceryl ester (PGD2-G), accounting for ~50% of its hydrolytic metabolism; CES1 knockdown or pharmacological inhibition (CPO, WWL113, WWL229) stabilizes PGD2-G, augmenting its anti-inflammatory effects (reduced IL-6, TNFα) upon LPS stimulation; PGD2-G (and/or downstream metabolites) activates PPARγ, altering alternative macrophage activation; inhibitor potency rank order: CPO > WWL113 > WWL229. THP-1 cell CES1 knockdown (siRNA), CES1 inhibitor dose-response, LC-MS/MS metabolite quantification, cytokine ELISA, PPARγ activation assay ACS omega High 33225149
2021 Melatonin treatment restores CES1 expression in prostate cancer cells via epigenetic modification; restored CES1 expression reduces lipid droplet accumulation, induces ER stress-mediated apoptosis, and reduces intratumoral androgen synthesis; Ces1-knockout mice show increased PCa tumor growth, confirming CES1's tumor-suppressive role via lipid metabolism regulation. Animal CRPC models, PCa cell lines, Ces1-/- mouse model, lipid droplet quantification, apoptosis assays, androgen synthesis measurement, epigenetic assays Clinical and translational medicine Medium 34185414
2021 CES1 G143E heterozygous carriers show 30.9% lower enalaprilat Cmax and 27.5% lower enalaprilat AUC0-∞ at steady state compared to non-carriers; carriers also showed no statistically significant blood pressure reduction vs ~12.4% reduction in non-carriers, directly linking CES1 loss-of-function to impaired prodrug activation and pharmacodynamic effect in vivo. Prospective multi-dose PK/PD clinical study, LC-MS/MS quantification, blood pressure monitoring British journal of clinical pharmacology High 33963573
2022 TMAO (trimethylamine N-oxide) increases Ces1 protein expression and activity in mouse liver and HepG2 cells via a NOX-dependent ROS/Nrf2/CES1 pathway, leading to increased clopidogrel hydrolysis (inactivation) and impaired platelet response; co-administration of TMAO-synthesis inhibitor (3,3-dimethyl-1-butanol), antioxidant (N-acetyl-L-cysteine), or Nrf2 inhibitor (ML385) reversed these effects. Mouse dietary TMAO/choline feeding, pharmacological pathway dissection (FMO inhibitor, antioxidant, Nrf2 inhibitor), HepG2 cell treatment, Ces1 protein/activity measurement, clopidogrel metabolite LC-MS/MS, platelet aggregation assay Journal of thrombosis and haemostasis High 36695375
2023 CES1 inhibition (pharmacological or siRNA) in hepatocellular carcinoma cells alters lipid profiles by reducing polyunsaturated fatty acids (PUFAs), which activates PPARα/γ; loss of PPARα/γ activation downregulates the target gene SCD (involved in chemoresistance); the CES1-PPARα/γ-SCD axis sensitizes HCC cells to cisplatin, and co-administration of cisplatin with CES1 inhibition slows xenograft tumor growth. Pharmacological CES1 inhibition, siRNA knockdown, lipidomic analysis, PPARα/γ pathway analysis, SCD expression measurement, cisplatin sensitivity assays, xenograft mouse model JCI insight High 36472914
2023 G9a (Ehmt2-encoded histone methyltransferase) suppresses transcription of Ces1 in renal tubules; G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1; tubular-specific G9a knockout (Ehmt2Ksp) or G9a inhibition derepresses Ces1, reducing lipid accumulation and alleviating AKI; pharmacological Ces1 inhibition reverses the AKI-protective effect of Ehmt2Ksp mice, establishing a G9a/FXR-Ces1 axis controlling renal lipid homeostasis. Renal tubular-specific G9a knockout mice, pharmacological G9a inhibition, Ces1 pharmacological inhibition, chromatin binding assays (G9a vs FXR competition at Ces1 promoter), lipid staining, AKI model (I/R and cisplatin), atorvastatin and FXR agonist treatment EMBO reports High 37042626
2024 Nicotine activates CHRNA5 in head and neck squamous cell carcinoma cells, which physically interacts with CES1 (confirmed by co-immunoprecipitation and molecular docking); CHRNA5 activation via the MEK/ERK pathway upregulates CES1 expression; CHRNA5 knockdown reduces CES1 mRNA and protein levels, an effect reversed by nicotine exposure. Co-immunoprecipitation, molecular docking, immunofluorescence, CHRNA5 knockdown/overexpression, Western blot for p-MEK/MEK, p-ERK/ERK and CES1, nude mouse tumor formation assay Cell death & disease Medium 39472448
2018 CES1 in human lungs is present predominantly in the microsomal fraction with 30-50-fold higher Vmax for pNPA (CES1 marker substrate) compared to FD (CES2 marker); CES1 and CES2 show 2.5-5-fold and 8-15-fold inter-individual variation in lung hydrolytic activity, respectively, demonstrating CES1 as the dominant esterase in human lung tissue. Cytosol and microsomal fractionation of 20 human lung samples, kinetic assays (Vmax, Km), selective inhibitor studies (loperamide for CES2, BNPP, PMSF) Biochemical pharmacology High 29407485
2018 MiR-155 overexpression in THP-1 macrophages upregulates CES1 (CEH) mRNA and protein in a dose- and time-dependent manner; miR-155-mediated CEH induction reduces intracellular cholesteryl ester accumulation and foam cell formation; siRNA knockdown of CEH reverses miR-155's anti-foam cell effect; Tim-3 overexpression attenuates miR-155-mediated CEH induction, placing Tim-3 upstream of the miR-155/CES1 axis. miR-155 mimic transfection, siCEH knockdown, Tim-3 overexpression in THP-1 macrophages, cholesterol efflux assay, lipid accumulation quantification, RT-PCR and Western blot Biomedicine & pharmacotherapy Medium 29803178

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2005 Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. The Journal of clinical investigation 760 15931389
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2001 A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development (Cambridge, England) 248 11493519
2002 Current progress on esterases: from molecular structure to function. Drug metabolism and disposition: the biological fate of chemicals 241 11950776
2013 Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation 209 23467860
2003 Irinotecan pathway genotype analysis to predict pharmacokinetics. Clinical cancer research : an official journal of the American Association for Cancer Research 209 12960109
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2008 Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. American journal of human genetics 188 18485328
2007 Carboxylesterase in the liver and small intestine of experimental animals and human. Life sciences 170 17764701
2012 Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. The Journal of pharmacology and experimental therapeutics 166 23275066
2003 Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nature structural biology 166 12679808
2010 Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins. Mammalian genome : official journal of the International Mammalian Genome Society 146 20931200
1996 Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature 141 8700229
2003 Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chemistry & biology 136 12725862
2013 The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenetics and genomics 135 23111421
1991 A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. The Journal of biological chemistry 128 1918003
2008 Human carboxylesterases HCE1 and HCE2: ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin. Biochemical pharmacology 126 18983829
2006 Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1. Journal of molecular biology 117 16962139
2021 Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nature genetics 116 34857952
2004 Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug metabolism and disposition: the biological fate of chemicals 105 15100172
1999 The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein. Molecular cell 102 10518212
2009 Human carboxylesterases: an update on CES1, CES2 and CES3. Protein and peptide letters 100 19508181
2003 The Snail-like CES-1 protein of C. elegans can block the expression of the BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins. Development (Cambridge, England) 99 12874127
2000 Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA. Physiological genomics 99 11015575
2004 Pharmacogenomic assessment of carboxylesterases 1 and 2. Genomics 95 15475243
1993 Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. Biochemistry 95 8218228
2019 Carboxylesterase 1 and Precision Pharmacotherapy: Pharmacogenetics and Nongenetic Regulators. Drug metabolism and disposition: the biological fate of chemicals 92 31871135
2013 In vitro drug metabolism by human carboxylesterase 1: focus on angiotensin-converting enzyme inhibitors. Drug metabolism and disposition: the biological fate of chemicals 91 24141856
2009 Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma. Proteomics 89 19658107
1997 Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug metabolism and disposition: the biological fate of chemicals 86 9311626
2016 Age-Dependent Absolute Abundance of Hepatic Carboxylesterases (CES1 and CES2) by LC-MS/MS Proteomics: Application to PBPK Modeling of Oseltamivir In Vivo Pharmacokinetics in Infants. Drug metabolism and disposition: the biological fate of chemicals 85 27895113
2014 The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug metabolism and drug interactions 84 24988246
2003 Human carboxylesterase 1: from drug metabolism to drug discovery. Biochemical Society transactions 82 12773168
1997 The POU gene ceh-18 promotes gonadal sheath cell differentiation and function required for meiotic maturation and ovulation in Caenorhabditis elegans. Developmental biology 79 9405097
2004 Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 77 15188402
1994 Targeted mutations in the Caenorhabditis elegans POU homeo box gene ceh-18 cause defects in oocyte cell cycle arrest, gonad migration, and epidermal differentiation. Genes & development 75 7958868
2000 Overlapping roles of two Hox genes and the exd ortholog ceh-20 in diversification of the C. elegans postembryonic mesoderm. Development (Cambridge, England) 72 11060243
2000 The LIM homeobox gene ceh-14 confers thermosensory function to the AFD neurons in Caenorhabditis elegans. Neuron 70 10774727
2007 The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9. Genes & development 69 18056428
2006 Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans. Current biology : CB 69 16461282
2011 The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS biology 68 21713031
2002 Roles of the Homothorax/Meis/Prep homolog UNC-62 and the Exd/Pbx homologs CEH-20 and CEH-40 in C. elegans embryogenesis. Development (Cambridge, England) 65 12399316
1995 The C. elegans neuronally expressed homeobox gene ceh-10 is closely related to genes expressed in the vertebrate eye. Development (Cambridge, England) 63 7789259
2007 Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho. Genes & development 62 18056429
1999 Anterior organization of the Caenorhabditis elegans embryo by the labial-like Hox gene ceh-13. Development (Cambridge, England) 62 10068646
2016 Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. Drug metabolism and disposition: the biological fate of chemicals 59 26817948
2005 Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules). The American journal of surgical pathology 59 16160475
2000 The homeodomain protein CePHOX2/CEH-17 controls antero-posterior axonal growth in C. elegans. Development (Cambridge, England) 59 10887091
2009 Regulation of carboxylesterase 1 (CES1) in human adipose tissue. Biochemical and biophysical research communications 56 19332024
2015 CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors. The pharmacogenomics journal 53 26076923
2006 Direct regulation of egl-1 and of programmed cell death by the Hox protein MAB-5 and by CEH-20, a C. elegans homolog of Pbx1. Development (Cambridge, England) 53 16421192
2002 Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13. Developmental biology 53 11820809
2007 UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes & development 49 17289921
2019 Synthesis of clathrate cerium superhydride CeH9 at 80-100 GPa with atomic hydrogen sublattice. Nature communications 48 31575861
2016 Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. Drug metabolism and disposition: the biological fate of chemicals 48 26825642
2010 A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obesity facts 48 20975297
2005 ceh-16/engrailed patterns the embryonic epidermis of Caenorhabditis elegans. Development (Cambridge, England) 48 15659483
2005 Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2). Drug metabolism and disposition: the biological fate of chemicals 45 16033949
2001 Regulation of ectodermal and excretory function by the C. elegans POU homeobox gene ceh-6. Development (Cambridge, England) 45 11171402
2019 CEH-60/PBX and UNC-62/MEIS Coordinate a Metabolic Switch that Supports Reproduction in C. elegans. Developmental cell 42 30956009
2018 The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty. Pharmacogenomics and personalized medicine 42 30100750
2009 The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function in C. elegans mesoderm development. Development (Cambridge, England) 42 19605496
2021 Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1. Clinical and translational medicine 41 34185414
2017 The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects. British journal of clinical pharmacology 38 28087982
2004 The C. elegans ceh-36 gene encodes a putative homemodomain transcription factor involved in chemosensory functions of ASE and AWC neurons. Journal of molecular biology 38 15095973
2001 The Caenorhabditis elegans Six/sine oculis class homeobox gene ceh-32 is required for head morphogenesis. Developmental biology 38 11476572
1997 The expression of the C. elegans labial-like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity. Development (Cambridge, England) 38 9334268
2010 The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans. Development (Cambridge, England) 37 20150279
2010 Depot-specific expression of lipolytic genes in human adipose tissues--association among CES1 expression, triglyceride lipase activity and adiposity. Journal of atherosclerosis and thrombosis 35 21081832
2009 Es-x/Ces1 prevents triacylglycerol accumulation in McArdle-RH7777 hepatocytes. Biochimica et biophysica acta 35 19651238
2023 Interfering with lipid metabolism through targeting CES1 sensitizes hepatocellular carcinoma for chemotherapy. JCI insight 33 36472914
2018 Presence and inter-individual variability of carboxylesterases (CES1 and CES2) in human lung. Biochemical pharmacology 33 29407485
2019 Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway. Digestive diseases and sciences 32 31076985
2023 Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1. EMBO reports 30 37042626
2015 CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease. Journal of neurosurgery 29 26587656
2013 Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene. Journal of child and adolescent psychopharmacology 29 24350812
2007 Haplotypes and a novel defective allele of CES2 found in a Japanese population. Drug metabolism and disposition: the biological fate of chemicals 29 17640957
2003 The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3 pharynx motoneuron function. Development (Cambridge, England) 29 12810585
2018 Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis. Biochimica et biophysica acta. Molecular and cell biology of lipids 28 29631096
2015 The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development. PLoS genetics 28 25738873
2022 The enteric nervous system of the C. elegans pharynx is specified by the Sine oculis-like homeobox gene ceh-34. eLife 27 35324425
2018 Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis. Antimicrobial agents and chemotherapy 27 29263072
2009 The C. elegans engrailed homolog ceh-16 regulates the self-renewal expansion division of stem cell-like seam cells. Developmental biology 24 19607822
2020 Natural Products as Modulators of CES1 Activity. Drug metabolism and disposition: the biological fate of chemicals 23 32591414
2017 Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans. Aging cell 23 28560849
2005 Altered expression of TFF-1 and CES-2 in Barrett's Esophagus and associated adenocarcinomas. Neoplasia (New York, N.Y.) 23 15967118
2019 Influence of CYP450 Enzymes, CES1, PON1, ABCB1, and P2RY12 Polymorphisms on Clopidogrel Response in Patients Subjected to a Percutaneous Neurointervention. Clinical therapeutics 22 31128980
2017 Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr -/- mice. Scientific reports 22 29259301
2014 CES2, ABCG2, TS and Topo-I primary and synchronous metastasis expression and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI regimen. International journal of molecular sciences 22 25198900
2007 Transcriptional regulation of AQP-8, a Caenorhabditis elegans aquaporin exclusively expressed in the excretory system, by the POU homeobox transcription factor CEH-6. The Journal of biological chemistry 22 17660295
2018 MiR-155 inhibits transformation of macrophages into foam cells via regulating CEH expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29803178
2022 The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In Vitro. Drug metabolism and disposition: the biological fate of chemicals 20 35790245
2015 Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics. Pharmacogenomics 20 25896426
2013 Relationship between CES2 genetic variations and rifampicin metabolism. The Journal of antimicrobial chemotherapy 20 23471941
2010 Carboxylesterase 1 (Ces1): from monocyte marker to major player. Journal of clinical pathology 20 21177752
2024 Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway. Cell death & disease 19 39472448
2020 Effect of Sex, Use of Pantoprazole and Polymorphisms in SLC22A1, ABCB1, CES1, CYP3A5 and CYP2D6 on the Pharmacokinetics and Safety of Dabigatran. Advances in therapy 19 32564268
2016 Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus. Pharmacogenetics and genomics 19 26871237
2010 The C. elegans Hox gene ceh-13 regulates cell migration and fusion in a non-colinear way. Implications for the early evolution of Hox clusters. BMC developmental biology 19 20667114
2009 Two Hox cofactors, the Meis/Hth homolog UNC-62 and the Pbx/Exd homolog CEH-20, function together during C. elegans postembryonic mesodermal development. Developmental biology 19 19643105
2009 Relations between strain and gender dependencies of irinotecan toxicity and UGT1A1, CES2 and TOP1 expressions in mice. Toxicology letters 19 19931604
2023 The homeodomain transcription factor CEH-37 regulates PMK-1/p38 MAPK pathway to protect against intestinal infection via the phosphatase VHP-1. Cellular and molecular life sciences : CMLS 18 37796333
2013 The LIM homeobox gene ceh-14 is required for phasmid function and neurite outgrowth. Developmental biology 18 23608457
2020 Effect of CES1 and ABCB1 genotypes on the pharmacokinetics and clinical outcomes of dabigatran etexilate in patients with atrial fibrillation and chronic kidney disease. Drug metabolism and personalized therapy 17 32134727
2020 Inactivation of CES1 Blocks Prostaglandin D2 Glyceryl Ester Catabolism in Monocytes/Macrophages and Enhances Its Anti-inflammatory Effects, Whereas the Pro-inflammatory Effects of Prostaglandin E2 Glyceryl Ester Are Attenuated. ACS omega 17 33225149
2019 The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios. Basic & clinical pharmacology & toxicology 17 30801959
2017 The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. Basic & clinical pharmacology & toxicology 17 28639420
2013 Coordination of cell proliferation and cell fate determination by CES-1 snail. PLoS genetics 17 24204299
2003 Twelve novel single nucleotide polymorphisms in the CES2 gene encoding human carboxylesterase 2 (hCE-2). Drug metabolism and pharmacokinetics 17 15618752
2001 The Caenorhabditis elegans distal-less ortholog ceh-43 is required for development of the anterior hypodermis. Developmental dynamics : an official publication of the American Association of Anatomists 17 11747075
1998 Effects of deletion mutations in the yeast Ces1 protein on cell growth and morphology and on high copy suppression of mutations in mRNA capping enzyme and translation initiation factor 4A. Nucleic acids research 17 9443973
2022 Choline and trimethylamine N-oxide impair metabolic activation of and platelet response to clopidogrel through activation of the NOX/ROS/Nrf2/CES1 pathway. Journal of thrombosis and haemostasis : JTH 16 36695375
2021 Enhancer RNA lnc-CES1-1 inhibits decidual cell migration by interacting with RNA-binding protein FUS and activating PPARγ in URPL. Molecular therapy. Nucleic acids 16 33738142
2015 Fluoxetine reduces CES1, CES2, and CYP3A4 expression through decreasing PXR and increasing DEC1 in HepG2 cells. Xenobiotica; the fate of foreign compounds in biological systems 16 26340669
2013 Clinical implications of CES2 RNA expression in neuroblastoma. Journal of pediatric surgery 16 23480903
2009 Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA. Genes and immunity 16 19458622
2004 An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the Forkhead factor PHA-4. Developmental biology 16 14738885
2003 Sequence-specific binding to telomeric DNA by CEH-37, a homeodomain protein in the nematode Caenorhabditis elegans. The Journal of biological chemistry 16 12711598
2021 CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop. Molecular metabolism 15 34971802
2020 PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning. PLoS genetics 15 32946434
2019 CEH-60/PBX regulates vitellogenesis and cuticle permeability through intestinal interaction with UNC-62/MEIS in Caenorhabditis elegans. PLoS biology 15 31675356
2017 Single-nucleotide polymorphisms in the genes of CES2, CDA and enzymatic activity of CDA for prediction of the efficacy of capecitabine-containing chemotherapy in patients with metastatic breast cancer. Pharmacological research 15 28827188
2020 Genetic Analysis Reveals a Significant Contribution of CES1 to Prostate Cancer Progression in Taiwanese Men. Cancers 14 32466188
2001 Multiple enhancers contribute to expression of the NK-2 homeobox gene ceh-22 in C. elegans pharyngeal muscle. Genesis (New York, N.Y. : 2000) 14 11783006
2021 Effect of CES1 genetic variation on enalapril steady-state pharmacokinetics and pharmacodynamics in healthy subjects. British journal of clinical pharmacology 13 33963573