PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33626394-6 2021 SIGNIFICANCE: Short-term standard alcohol consumption would significantly enhance suppression of ADP-induced platelet aggregation and activation by clopidogrel through significant inhibition of Nrf2/Ces1 signaling pathway and induction of Cyp2c, suggesting that alcohol may interact with drugs that are predominantly metabolized by CES1 or CYP2C in patient care, including clopidogrel. Clopidogrel 148-159 carboxylesterase 1 Homo sapiens 199-203 33626394-6 2021 SIGNIFICANCE: Short-term standard alcohol consumption would significantly enhance suppression of ADP-induced platelet aggregation and activation by clopidogrel through significant inhibition of Nrf2/Ces1 signaling pathway and induction of Cyp2c, suggesting that alcohol may interact with drugs that are predominantly metabolized by CES1 or CYP2C in patient care, including clopidogrel. Clopidogrel 148-159 carboxylesterase 1 Homo sapiens 332-336 30911318-8 2019 Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel. Clopidogrel 140-151 carboxylesterase 1 Homo sapiens 18-36 31560647-0 2019 Effects of the rs2244613 polymorphism of the CES1 gene on the antiplatelet effect of the receptor P2Y12 blocker clopidogrel. Clopidogrel 112-123 carboxylesterase 1 Homo sapiens 45-49 31560647-1 2019 Background The aim of this study was to evaluate the association of the carriage of the rs2244613 polymorphism of the CES1 gene with clopidogrel resistance as well as to evaluate the effectiveness of antiplatelet therapy in the carriers of this marker who have had acute coronary syndrome (ACS). Clopidogrel 133-144 carboxylesterase 1 Homo sapiens 118-122 31175950-1 2019 Human carboxylesterase 1 (CES1), primarily expressed in the liver and adipocytes, is responsible for the hydrolysis of endogenous esters (such as cholesteryl esters and triacylglycerols) and the metabolism of xenobiotic esters (such as clopidogrel and oseltamivir), thus participates in physiological and pathological processes. Clopidogrel 236-247 carboxylesterase 1 Homo sapiens 6-24 31175950-1 2019 Human carboxylesterase 1 (CES1), primarily expressed in the liver and adipocytes, is responsible for the hydrolysis of endogenous esters (such as cholesteryl esters and triacylglycerols) and the metabolism of xenobiotic esters (such as clopidogrel and oseltamivir), thus participates in physiological and pathological processes. Clopidogrel 236-247 carboxylesterase 1 Homo sapiens 26-30 33519456-9 2020 Clopidogrel resistance by DM was the integrated effects of altered K t,i, CYP2C19, CYP3A4, CES1 and k irre. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 91-95 31039046-0 2020 Inhibition of carboxylesterase-1 alters clopidogrel metabolism and disposition. Clopidogrel 40-51 carboxylesterase 1 Homo sapiens 14-32 31039046-2 2020 Most research has focused on the role of hepatic CYP450 metabolism as the primary source of response variability despite 85-90% of clopidogrel being hydrolyzed by human carboxylesterase-1 (CES1). Clopidogrel 131-142 carboxylesterase 1 Homo sapiens 169-187 31039046-2 2020 Most research has focused on the role of hepatic CYP450 metabolism as the primary source of response variability despite 85-90% of clopidogrel being hydrolyzed by human carboxylesterase-1 (CES1). Clopidogrel 131-142 carboxylesterase 1 Homo sapiens 189-193 31039046-3 2020 The purpose of this study is to determine the effects of the known CES1 inhibitor alcohol on clopidogrel metabolism: (1) in vitro in human recombinant CES1 and human liver S9 (HLS9) fractions and (2) in a plasma carboxylesterase deficient mouse (Es1e) strain administered 25 mg/kg oral clopidogrel alone and with 3 g/kg alcohol. Clopidogrel 93-104 carboxylesterase 1 Homo sapiens 67-71 31039046-3 2020 The purpose of this study is to determine the effects of the known CES1 inhibitor alcohol on clopidogrel metabolism: (1) in vitro in human recombinant CES1 and human liver S9 (HLS9) fractions and (2) in a plasma carboxylesterase deficient mouse (Es1e) strain administered 25 mg/kg oral clopidogrel alone and with 3 g/kg alcohol. Clopidogrel 286-297 carboxylesterase 1 Homo sapiens 67-71 31039046-7 2020 Clopidogrel metabolism is highly sensitive to alterations in CES1 activity. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 61-65 30911318-10 2019 Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel. Clopidogrel 183-194 carboxylesterase 1 Homo sapiens 67-85 29382249-4 2019 CES1 activities were determined by monitoring the depletion of known substrate, the clopidogrel. Clopidogrel 84-95 carboxylesterase 1 Homo sapiens 0-4 27557470-5 2017 In addition, interindividual differences in the fraction absorbed and the CES1 activity were identified as sources of interindividual differences in clopidogrel"s active metabolite concentrations and, thus, platelet reactivity. Clopidogrel 149-160 carboxylesterase 1 Homo sapiens 74-78 30520344-2 2019 The purpose of this research is to describe the prevalence of pharmacogene variants associated with clopidogrel responsiveness (CYP2C19, B4GALT2, ABCB1, PON1, CES1 and P2RY12) in Hispanic/Latino patients of diverse backgrounds. Clopidogrel 100-111 carboxylesterase 1 Homo sapiens 159-163 28990360-7 2018 Conversely, the CES1 c.428G>A missense SNV (rs71647871) impaired the hydrolysis of clopidogrel, increased exposure to clopidogrel active metabolite and enhanced its antiplatelet effects. Clopidogrel 86-97 carboxylesterase 1 Homo sapiens 16-20 28990360-7 2018 Conversely, the CES1 c.428G>A missense SNV (rs71647871) impaired the hydrolysis of clopidogrel, increased exposure to clopidogrel active metabolite and enhanced its antiplatelet effects. Clopidogrel 121-132 carboxylesterase 1 Homo sapiens 16-20 29240983-1 2018 Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel acyl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 80-98 28775293-0 2017 Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients. Clopidogrel 37-48 carboxylesterase 1 Homo sapiens 10-28 28775293-1 2017 Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. Clopidogrel 49-60 carboxylesterase 1 Homo sapiens 0-18 28775293-1 2017 Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. Clopidogrel 49-60 carboxylesterase 1 Homo sapiens 20-24 28775293-2 2017 The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. Clopidogrel 47-58 carboxylesterase 1 Homo sapiens 15-19 28775293-4 2017 The results showed that there was a significant association between CES1 S75N (rs2307240) and the outcome of clopidogrel therapy. Clopidogrel 109-120 carboxylesterase 1 Homo sapiens 68-72 28164519-1 2016 BACKGROUND: Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Clopidogrel 12-23 carboxylesterase 1 Homo sapiens 203-220 27196064-1 2016 The major metabolic pathway of clopidogrel is conversion to carboxylic acid by an esterase (CES1), forming clopidogrelic acid (SR26334) that is inactive. Clopidogrel 31-42 carboxylesterase 1 Homo sapiens 92-96 28164519-1 2016 BACKGROUND: Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Clopidogrel 12-23 carboxylesterase 1 Homo sapiens 222-226 25704243-3 2015 Clopidogrel carboxylic acid to clopidogrel area under the plasma concentration-time curve from 0 hours to infinity (AUC0- ) ratio was 53% less in CES1 c.428G>A carriers than in noncarriers (P = 0.009), indicating impaired hydrolysis of clopidogrel. Clopidogrel 31-42 carboxylesterase 1 Homo sapiens 147-151 27450232-12 2016 CONCLUSIONS: For Chinese patients with symptomatic extracranial or intracranial stenosis treated with clopidogrel, CYP2C19*3 mutation was associated with an increased risk of ischemic events, and the mutation of rs8192950 in CES1 is associated with a decreased risk of recurrent ischemic events. Clopidogrel 102-113 carboxylesterase 1 Homo sapiens 225-229 26750665-6 2016 The results showed that pretreatment with GA potentiated clopidogrel-induced apoptosis by down-regulating CES1. Clopidogrel 57-68 carboxylesterase 1 Homo sapiens 106-110 25980448-2 2015 Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 21-39 25980448-2 2015 Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 41-45 25980448-12 2015 CONCLUSIONS: Following myocardial infarction, use of clopidogrel with ACE inhibitors activated by CES1 is not associated with an increased risk of adverse cardiovascular outcomes relative to lisinopril. Clopidogrel 53-64 carboxylesterase 1 Homo sapiens 98-102 25704243-0 2015 Carboxylesterase 1 c.428G>A single nucleotide variation increases the antiplatelet effects of clopidogrel by reducing its hydrolysis in humans. Clopidogrel 97-108 carboxylesterase 1 Homo sapiens 0-18 25704243-1 2015 Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. Clopidogrel 49-60 carboxylesterase 1 Homo sapiens 0-18 25704243-1 2015 Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. Clopidogrel 49-60 carboxylesterase 1 Homo sapiens 20-24 25704243-3 2015 Clopidogrel carboxylic acid to clopidogrel area under the plasma concentration-time curve from 0 hours to infinity (AUC0- ) ratio was 53% less in CES1 c.428G>A carriers than in noncarriers (P = 0.009), indicating impaired hydrolysis of clopidogrel. Clopidogrel 240-251 carboxylesterase 1 Homo sapiens 147-151 25704243-6 2015 In conclusion, the CES1 c.428G>A SNV increases clopidogrel active metabolite concentrations and antiplatelet effects by reducing clopidogrel hydrolysis to inactive metabolites. Clopidogrel 50-61 carboxylesterase 1 Homo sapiens 19-23 25704243-6 2015 In conclusion, the CES1 c.428G>A SNV increases clopidogrel active metabolite concentrations and antiplatelet effects by reducing clopidogrel hydrolysis to inactive metabolites. Clopidogrel 132-143 carboxylesterase 1 Homo sapiens 19-23 25747989-0 2015 Carboxylesterase 1-mediated drug-drug interactions between clopidogrel and simvastatin. Clopidogrel 59-70 carboxylesterase 1 Homo sapiens 0-18 26767297-2 2015 METHODS: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. Clopidogrel 97-108 carboxylesterase 1 Homo sapiens 13-17 26767297-2 2015 METHODS: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. Clopidogrel 260-271 carboxylesterase 1 Homo sapiens 13-17 26767297-6 2015 CONCLUSION: It is suggested that Fufang Danshen Dripping Pill has inhibitory effects on Clopidogrel metabolism enzymes target such as CES1, Cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6. Clopidogrel 88-99 carboxylesterase 1 Homo sapiens 134-138 25747989-3 2015 Both CYP enzymes and carboxylesterase 1 (CES1) are involved in the metabolism of clopidogrel, while CES1 is believed to be the enzyme responsible for the activation of simvastatin. Clopidogrel 81-92 carboxylesterase 1 Homo sapiens 21-39 25747989-3 2015 Both CYP enzymes and carboxylesterase 1 (CES1) are involved in the metabolism of clopidogrel, while CES1 is believed to be the enzyme responsible for the activation of simvastatin. Clopidogrel 81-92 carboxylesterase 1 Homo sapiens 41-45 25747989-6 2015 The present study addresses these inconsistencies by exploring the potential role of CES1 in the metabolism of clopidogrel and simvastatin. Clopidogrel 111-122 carboxylesterase 1 Homo sapiens 85-89 25222620-1 2014 Clopidogrel is an oral antiplatelet prodrug, the majority of which is hydrolyzed to an inactive metabolite by hepatic carboxylesterase 1 (CES1). Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 118-136 25222620-1 2014 Clopidogrel is an oral antiplatelet prodrug, the majority of which is hydrolyzed to an inactive metabolite by hepatic carboxylesterase 1 (CES1). Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 138-142 24988246-3 2014 Polymorphisms of the CES1 gene have been reported to affect the metabolism of dabigatran etexilate, methylphenidate, oseltamivir, imidapril, and clopidogrel, whereas variants of the CES2 gene have been found to affect aspirin and irinotecan. Clopidogrel 145-156 carboxylesterase 1 Homo sapiens 21-25 24535487-1 2014 OBJECTIVE: Carboxylesterase 1 hydrolyzes the majority of clopidogrel to the inactive metabolite. Clopidogrel 57-68 carboxylesterase 1 Homo sapiens 11-29 19704027-6 2009 Clopidogrel was largely hydrolyzed to an inactive acid metabolite (approximately 90% of total metabolites analyzed), and the clopidogrel concentrations consumed were correlated to human carboxylesterase 1 activity in each source of liver microsomes. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 186-204 22504157-7 2012 CES1 levels significantly correlated with hydrolysis of the CES1 substrates, clopidogrel (5 muM) and oxybutynin (10 muM), whereas CES2 levels correlated strongly with hydrolysis of the CES2 substrate, irinotecan (1 muM), indicating that quantified protein levels are highly reliable. Clopidogrel 77-88 carboxylesterase 1 Homo sapiens 0-4 23275066-0 2013 Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. Clopidogrel 39-50 carboxylesterase 1 Homo sapiens 0-18 23275066-2 2013 Clopidogrel, a recognized substrate of hepatic carboxylesterase 1 (CES1), undergoes extensive hydrolytic metabolism in the liver. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 47-65 23275066-2 2013 Clopidogrel, a recognized substrate of hepatic carboxylesterase 1 (CES1), undergoes extensive hydrolytic metabolism in the liver. Clopidogrel 0-11 carboxylesterase 1 Homo sapiens 67-71 23275066-4 2013 We determined whether CES1 inhibition and CES1 genetic polymorphisms would significantly influence the biotransformation of clopidogrel and alter the formation of the active metabolite. Clopidogrel 124-135 carboxylesterase 1 Homo sapiens 22-26 23275066-4 2013 We determined whether CES1 inhibition and CES1 genetic polymorphisms would significantly influence the biotransformation of clopidogrel and alter the formation of the active metabolite. Clopidogrel 124-135 carboxylesterase 1 Homo sapiens 42-46 23275066-5 2013 Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. Clopidogrel 16-27 carboxylesterase 1 Homo sapiens 37-41 23275066-5 2013 Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. Clopidogrel 155-166 carboxylesterase 1 Homo sapiens 37-41 23275066-5 2013 Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. Clopidogrel 155-166 carboxylesterase 1 Homo sapiens 37-41 23275066-6 2013 As anticipated, clopidogrel and 2-oxo-clopidogrel were efficiently hydrolyzed by the cell s9 fractions prepared from wild-type CES1 transfected cells. Clopidogrel 16-27 carboxylesterase 1 Homo sapiens 127-131 23275066-7 2013 The enzymatic activity of the CES1 variants G143E and D260fs were completely impaired in terms of catalyzing the hydrolysis of clopidogrel and 2-oxo-clopidogrel. Clopidogrel 127-138 carboxylesterase 1 Homo sapiens 30-34 23275066-9 2013 In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Clopidogrel 158-169 carboxylesterase 1 Homo sapiens 22-26 23275066-9 2013 In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Clopidogrel 158-169 carboxylesterase 1 Homo sapiens 61-65 23275066-9 2013 In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Clopidogrel 158-169 carboxylesterase 1 Homo sapiens 61-65 23275066-10 2013 Additionally, CES1 genetic variants have the potential to serve as a biomarker to predict clopidogrel response and individualize clopidogrel dosing regimens in clinical practice. Clopidogrel 90-101 carboxylesterase 1 Homo sapiens 14-18 23275066-10 2013 Additionally, CES1 genetic variants have the potential to serve as a biomarker to predict clopidogrel response and individualize clopidogrel dosing regimens in clinical practice. Clopidogrel 129-140 carboxylesterase 1 Homo sapiens 14-18 23111421-0 2013 The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Clopidogrel 80-91 carboxylesterase 1 Homo sapiens 32-50 23111421-0 2013 The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Clopidogrel 129-140 carboxylesterase 1 Homo sapiens 32-50 23111421-1 2013 INTRODUCTION: Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. Clopidogrel 89-100 carboxylesterase 1 Homo sapiens 14-32 23111421-1 2013 INTRODUCTION: Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. Clopidogrel 89-100 carboxylesterase 1 Homo sapiens 34-38 23111421-2 2013 METHODS: We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. Clopidogrel 211-222 carboxylesterase 1 Homo sapiens 46-50 23111421-2 2013 METHODS: We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. Clopidogrel 299-310 carboxylesterase 1 Homo sapiens 46-50 23111421-3 2013 RESULTS: The levels of clopidogrel active metabolite were significantly greater in CES1 143E-allele carriers (P=0.001). Clopidogrel 23-34 carboxylesterase 1 Homo sapiens 83-87 23111421-4 2013 Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P=0.003) and clopidogrel-treated coronary heart disease patients (P=0.03). Clopidogrel 93-104 carboxylesterase 1 Homo sapiens 60-64 23111421-4 2013 Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P=0.003) and clopidogrel-treated coronary heart disease patients (P=0.03). Clopidogrel 218-229 carboxylesterase 1 Homo sapiens 60-64 23111421-6 2013 CONCLUSION: Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel. Clopidogrel 154-165 carboxylesterase 1 Homo sapiens 98-102 19704027-6 2009 Clopidogrel was largely hydrolyzed to an inactive acid metabolite (approximately 90% of total metabolites analyzed), and the clopidogrel concentrations consumed were correlated to human carboxylesterase 1 activity in each source of liver microsomes. Clopidogrel 125-136 carboxylesterase 1 Homo sapiens 186-204 16943252-9 2006 In addition, hydrolysis of clopidogrel among liver samples was correlated well with the level of HCE1, and hydrolysis of aspirin with HCE2. Clopidogrel 27-38 carboxylesterase 1 Homo sapiens 97-101 16943252-0 2006 Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. Clopidogrel 32-43 carboxylesterase 1 Homo sapiens 71-88 16943252-8 2006 Consistent with the tissue distribution of two carboxylesterases human carboxylesterase (HCE) 1 and HCE2, recombinant HCE1 hydrolyzed clopidogrel, whereas recombinant HCE2 hydrolyzed aspirin. Clopidogrel 134-145 carboxylesterase 1 Homo sapiens 118-122