{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:26:40Z","timestamp":1779920800917,"version":"3.53.1"},"reference-count":42,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF)","award":["1711187922"],"award-info":[{"award-number":["1711187922"]}]},{"name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF)","award":["119010032CG000"],"award-info":[{"award-number":["119010032CG000"]}]},{"name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry","award":["1711187922"],"award-info":[{"award-number":["1711187922"]}]},{"name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry","award":["119010032CG000"],"award-info":[{"award-number":["119010032CG000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exposure to tamoxifen can exert effects on the human liver, and esterases process prodrugs such as antibiotics and convert them to less toxic metabolites. In this study, the porcine liver esterase (PLE)-inhibitory activity of tamoxifen has been investigated. PLE showed inhibition of a PLE isoenzyme (PLE5). In addition, avenanthramides, which have a similar structure to that of tamoxifen, have been used to determine the PLE-inhibitory effect. Among the avenanthramide derivatives, avenanthramide B has been shown to inhibit PLE. Avenanthramide B interacts with Lys284 of PLE, whereas avenanthramide A and C counteract with Lys284. Avenanthramide B has shown a similar inhibitory effect to that of tamoxifen. Given that avenanthramide B can modulate the action of PLE, it can be used in pharmaceutical and industrial applications for modulating the effects of PLE. Based on superimposed structures between PLE and human liver esterase, the impact of tamoxifen use in humans is discussed. In addition, this study can serve as a fundamental basis for future investigations regarding the potential risk of tamoxifen and other drugs. Thus, this study presents an insight into the comparison of structurally similar tamoxifen and avenanthramides on liver esterases, which can have implications for the pharmaceutical and agricultural industries.<\/jats:p>","DOI":"10.3390\/ijms252413291","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T06:44:05Z","timestamp":1733899445000},"page":"13291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Compared Inhibitory Activities of Tamoxifen and Avenanthramide B on Liver Esterase and Correlation Based on the Superimposed Structure Between Porcine and Human Liver Esterase"],"prefix":"10.3390","volume":"25","author":[{"given":"Hakseong","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Biological Science, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-5259","authenticated-orcid":false,"given":"Sungbo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Advanced Predictive Research, Center for Biomimetic Research, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hak","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Bacterial Disease Research, Center for Infectious Disease Research, Korea National Institute of Health, Cheongju 28159, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Seok","family":"Bak","sequence":"additional","affiliation":[{"name":"Department of Emergency Medical Services, Sun Moon University, Asan-si 31460, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong-Suk","family":"Yang","sequence":"additional","affiliation":[{"name":"National Institute for Nanomaterials Technology (NINT), POSTECH, Pohang 37673, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-5849","authenticated-orcid":false,"given":"Daeui","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Advanced Predictive Research, Center for Biomimetic Research, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-0714","authenticated-orcid":false,"given":"Cheorl-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.2174\/092986706776360969","article-title":"Carboxylesterases-detoxifying enzymes and targets for drug therapy","volume":"13","author":"Potter","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jbt.20178","article-title":"Human carboxylesterases and their role in xenobiotic and endobiotic metabolism","volume":"21","author":"Ross","year":"2007","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cbi.2006.07.001","article-title":"Structure, function and regulation of carboxylesterases","volume":"162","author":"Satoh","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00335-010-9284-4","article-title":"Recommended nomenclature for five mammalian carboxylesterase gene families: Human, mouse, and rat genes and proteins","volume":"21","author":"Holmes","year":"2010","journal-title":"Mamm. Genome"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1097\/FPC.0b013e3283656bc1","article-title":"Pharm GKB summary: Tamoxifen pathway, pharmacokinetics","volume":"23","author":"Klein","year":"2013","journal-title":"Pharmacogenet Genom."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Xiao, Q., Zhang, Y., Wang, X., Xiao, Y., and Shi, D. (2019). Pig liver esterases PLE1 and PLE6: Heterologous expression, hydrolysis of common antibiotics and pharmacological consequences. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-51580-4"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1128\/JVI.02699-12","article-title":"The acetyl-esterase activity of the hemagglutinin-esterase protein of human coronavirus OC43 strongly enhances the production of infectious virus","volume":"687","author":"Desforges","year":"2013","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG) (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet, 365, 1687\u20131717.","DOI":"10.1016\/S0140-6736(05)66544-0"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.steroids.2007.07.009","article-title":"New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer","volume":"72","author":"Jordan","year":"2007","journal-title":"Steroids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/0006-2952(91)90172-2","article-title":"Evidence for superoxide formation during hepatic metabolism of tamoxifen","volume":"41","author":"Turner","year":"1991","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/tpj.2014.34","article-title":"Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer","volume":"15","author":"Lim","year":"2015","journal-title":"Pharmacogenomics J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jmb.2005.07.016","article-title":"Structural insights into drug processing by human carboxylesterase 1: Tamoxifen, mevastatin, and inhibition by benzil","volume":"352","author":"Fleming","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_13","first-page":"766","article-title":"Identification of two tamoxifen target proteins by photolabeling with 4-(2-morpholinoethoxy) benzophenone","volume":"13","author":"Sebbar","year":"2022","journal-title":"Bioconjugate Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.chemosphere.2015.01.002","article-title":"Tamoxifen ecotoxicity and resulting risks for aquatic ecosystems","volume":"128","author":"Orias","year":"2015","journal-title":"Chemosphere"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"124705","DOI":"10.1016\/j.chemosphere.2019.124705","article-title":"Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish","volume":"239","author":"Yu","year":"2020","journal-title":"Chemosphere"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-018-0577-5","article-title":"Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer","volume":"11","author":"Liu","year":"2018","journal-title":"Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s00394-008-0698-7","article-title":"Oat: Unique among the cereals","volume":"47","author":"Khan","year":"2008","journal-title":"Eur. J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1021\/jf103938e","article-title":"Chemical characterization of the avenanthramide-rich extract from oat and its effect on D-galactose-induced oxidative stress in mice","volume":"59","author":"Ren","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/jn\/134.6.1459","article-title":"Avenanthramides and phenolic acids from oats are bioavailable and act synergistically with vitamin C to enhance hamster and human LDL resistance to oxidation","volume":"134","author":"Chen","year":"2004","journal-title":"J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ijbiomac.2022.05.009","article-title":"Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery","volume":"210","author":"Dileep","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Yan, B., Sun, W., Chen, Q., Xiao, Q., Xiao, Y., Wang, X., and Shi, D. (2021). Pig Liver Esterases Hydrolyze Endocannabinoids and Promote Inflammatory Response. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.670427"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S0009-2614(99)00874-X","article-title":"Fragment molecular orbital method: An approximate computational method for large molecules","volume":"313","author":"Kitaura","year":"1999","journal-title":"Chem. Phys. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/jcc.20496","article-title":"Pair interaction energy decomposition analysis","volume":"28","author":"Fedorov","year":"2007","journal-title":"J. Comput. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lim, H., Baek, A., Kim, J., Kim, M.S., Liu, J., Nam, K.Y., Yoon, Y., and No, K.T. (2020). Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73820-8"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.csbj.2019.08.004","article-title":"Investigation of Hot Spot Region in XIAP Inhibitor Binding Site by Fragment Molecular Orbital Method","volume":"17","author":"Lim","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1021\/ct100684s","article-title":"DFTB3: Extension of the Self-Consistent-Charge Density-Functional Tight-Binding Method (SCC-DFTB)","volume":"7","author":"Gaus","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1021\/acsomega.8b00175","article-title":"Use of the multilayer fragment molecular orbital method to predict the rank order of protein\u2013ligand binding affinities: A case study using tankyrase 2 inhibitor","volume":"3","author":"Okimoto","year":"2018","journal-title":"ACS Omega"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1124\/dmd.111.039628","article-title":"Characterization of recombinant human carboxylesterases: Fluorescein diacetate as a probe substrate for human carboxylesterase 2","volume":"39","author":"Wang","year":"2011","journal-title":"Drug. Metab. Dispos."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-004-4384-z","article-title":"Effects of toremifene (TOR) and tamoxifen (TAM) on serum lipids in postmenopausal patients with breast cancer","volume":"88","author":"Kusama","year":"2004","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6438","DOI":"10.1021\/jf2002427","article-title":"Avenanthramides are bioavailable and accumulate in hepatic, cardiac, and skeletal muscle tissue following oral gavage in rats","volume":"59","author":"Koenig","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, G., Xu, L., Zhang, H., Liu, J., Yan, J., and Yan, Y. (2020). A De Novo Designed Esterase with p-Nitrophenyl Acetate Hydrolysis Activity. Molecules, 25.","DOI":"10.3390\/molecules25204658"},{"key":"ref_32","unstructured":"(2024, December 04). Crystal Structure of Human Liver Carboxylesterase 1 in Complex with Tamoxifen. Available online: https:\/\/pdbj.org\/emnavi\/quick.php?id=pdb-1ya4."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"154102","DOI":"10.1063\/5.0005188","article-title":"Recent developments in the general atomic and molecular electronic structure system","volume":"152","author":"Barca","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8432","DOI":"10.1039\/C7CP08185E","article-title":"New tricks for old dogs: Improving the accuracy of biomolecular force fields by pair-specific corrections to non-bonded interactions","volume":"20","author":"Yoo","year":"2018","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N log (N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models","volume":"13","author":"Miyamoto","year":"1992","journal-title":"J. Comput. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS","volume":"17","author":"Valiente","year":"2021","journal-title":"J. Chem. Theory Comput."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:52:21Z","timestamp":1760115141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":42,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413291"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413291","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,11]]}}}