{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:33:15Z","timestamp":1792809195466,"version":"4.5.0"},"reference-count":113,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974530"],"award-info":[{"award-number":["81974530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.ejmech.2025.118317","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:21:35Z","timestamp":1761672095000},"page":"118317","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"P2","title":["Lunasin: Exploring the pharmacological potential of a soy-derived peptide"],"prefix":"10.1016","volume":"302","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7458-5898","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuowei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Thu","family":"Hien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkin","family":"Musabaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khrystyna","family":"Pronyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118317_bib1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10118-022-2688-2","article-title":"Helical nonfouling polypeptides for biomedical applications","volume":"40","author":"Zhang","year":"2022","journal-title":"Chin. J. Polym. Sci."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118317_bib2","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202001974","article-title":"Polypeptides-drug conjugates for anticancer therapy","volume":"10","author":"Zhang","year":"2021","journal-title":"Adv. Healthcare Mater."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118317_bib3","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41569-020-0381-0","article-title":"Cardiac natriuretic peptides","volume":"17","author":"Goetze","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib4","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1096\/fj.201802251R","article-title":"Lunasin attenuates oxidant-induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE-\/- mice by up-regulating heme oxygenase-1 via PI3K\/Akt\/Nrf2\/ARE pathway","volume":"33","author":"Gu","year":"2019","journal-title":"FASEB J."},{"key":"10.1016\/j.ejmech.2025.118317_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2023.122180","article-title":"Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders","volume":"333","author":"Huang","year":"2023","journal-title":"Life Sci."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118317_bib6","doi-asserted-by":"crossref","first-page":"9187","DOI":"10.3390\/ijms24119187","article-title":"Lunasin and its epigenetic impact in cancer chemoprevention","volume":"24","author":"Kaufman-Szymczyk","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2025.118317_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.jnutbio.2023.109383","article-title":"Lunasin reduces the susceptibility of IL-10 deficient mice to inflammatory bowel disease and modulates the activation of the NLRP3 inflammasome","volume":"119","author":"Nieto-Veloza","year":"2023","journal-title":"J. Nutr. Biochem."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib8","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.3390\/plants12102011","article-title":"Contribution of proteins and peptides to the impact of a soy protein isolate on oxidative stress and inflammation-associated biomarkers in an innate immune cell model","volume":"12","author":"Franca-Oliveira","year":"2023","journal-title":"Plants"},{"issue":"5","key":"10.1016\/j.ejmech.2025.118317_bib9","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.3390\/nu15051220","article-title":"Evaluation of the multifunctionality of soybean proteins and peptides in immune cell models","volume":"15","author":"Paterson","year":"2023","journal-title":"Nutrients"},{"issue":"12","key":"10.1016\/j.ejmech.2025.118317_bib10","doi-asserted-by":"crossref","DOI":"10.1002\/mnfr.202001034","article-title":"Lunasin peptide is a modulator of the immune response in the human gastrointestinal tract","volume":"65","author":"Fern\u00e1ndez-Tom\u00e9","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Targeted Ther."},{"issue":"15","key":"10.1016\/j.ejmech.2025.118317_bib12","doi-asserted-by":"crossref","first-page":"10377","DOI":"10.1021\/acs.chemrev.7b00100","article-title":"Virus-derived peptides for clinical applications","volume":"117","author":"Yang","year":"2017","journal-title":"Chem. Rev."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118317_bib13","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1016\/S0021-9258(18)60989-5","article-title":"Amino acid sequence of a soybean (Glycine max) seed polypeptide having a poly(L-aspartic acid) structure","volume":"262","author":"Odani","year":"1987","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2025.118317_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2021.130220","article-title":"Utilization of tofu processing wastewater as a source of the bioactive peptide lunasin","volume":"362","author":"Nieto-Veloza","year":"2021","journal-title":"Food Chem."},{"key":"10.1016\/j.ejmech.2025.118317_bib15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tifs.2019.06.016","article-title":"Soy whey: more than just wastewater from tofu and soy protein isolate industry","volume":"91","author":"Chua","year":"2019","journal-title":"Trends Food Sci. Technol."},{"key":"10.1016\/j.ejmech.2025.118317_bib16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.foodres.2018.12.029","article-title":"Current state of art after twenty years of the discovery of bioactive peptide lunasin","volume":"116","author":"Fern\u00e1ndez-Tom\u00e9","year":"2019","journal-title":"Food Res. Int."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118317_bib17","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3390\/nu13051618","article-title":"Potential health benefits associated with lunasin concentration in dietary supplements and lunasin-enriched soy extract","volume":"13","author":"Gonzalez de Mejia","year":"2021","journal-title":"Nutrients"},{"issue":"12","key":"10.1016\/j.ejmech.2025.118317_bib18","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1002\/jsfa.8278","article-title":"Detection of lunasin in quinoa (Chenopodium quinoa willd.) and the in vitro evaluation of its antioxidant and anti-inflammatory activities","volume":"97","author":"Ren","year":"2017","journal-title":"J. Sci. Food Agric."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib19","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.3390\/nu14061188","article-title":"Legume proteins and peptides as compounds in nutraceuticals: a structural basis for dietary health effects","volume":"14","author":"Carbonaro","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.ejmech.2025.118317_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2021.130220","article-title":"Utilization of tofu processing wastewater as a source of the bioactive peptide lunasin","volume":"362","author":"Nieto-Veloza","year":"2021","journal-title":"Food Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118317_bib21","doi-asserted-by":"crossref","first-page":"C539","DOI":"10.1111\/j.1750-3841.2012.02676.x","article-title":"Analysis of lunasin in commercial and pilot plant produced soybean products and an improved method of lunasin purification","volume":"77","author":"Cavazos","year":"2012","journal-title":"J. Food Sci."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiosc.2018.01.013","article-title":"Tandem repeated expression of lunasin gene in Pichia pastoris and its anti-inflammatory activity in vitro","volume":"126","author":"Zhu","year":"2018","journal-title":"J. Biosci. Bioeng."},{"issue":"17","key":"10.1016\/j.ejmech.2025.118317_bib23","doi-asserted-by":"crossref","first-page":"9548","DOI":"10.3390\/ijms23179548","article-title":"Lunasin as a promising plant-derived peptide for cancer therapy","volume":"23","author":"Alves de Souza","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib24","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.3892\/ol.2017.6017","article-title":"Lunasin: a promising polypeptide for the prevention and treatment of cancer","volume":"13","author":"Wan","year":"2017","journal-title":"Oncol. Lett."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib25","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1016\/j.peptides.2011.09.009","article-title":"Differential gene expression of RAW 264.7 macrophages in response to the RGD peptide lunasin with and without lipopolysaccharide stimulation","volume":"32","author":"Dia","year":"2011","journal-title":"Peptides"},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib26","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/mnfr.201200301","article-title":"RGD-Peptide lunasin inhibits Akt-mediated NF-\u03baB activation in human macrophages through interaction with the \u03b1V\u03b23 integrin","volume":"56","author":"Cam","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"issue":"9","key":"10.1016\/j.ejmech.2025.118317_bib27","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.3390\/nu10091211","article-title":"Soybean bioactive peptides and their functional properties","volume":"10","author":"Chatterjee","year":"2018","journal-title":"Nutrients"},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib28","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/mnfr.200900073","article-title":"Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3","volume":"54","author":"de Mejia","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"issue":"13","key":"10.1016\/j.ejmech.2025.118317_bib29","doi-asserted-by":"crossref","first-page":"6940","DOI":"10.1021\/jf200183m","article-title":"Lunasin and bowman-birk protease inhibitor concentrations of protein extracts from enzyme-assisted aqueous extraction of soybeans","volume":"59","author":"Leite Nobrega de Moura","year":"2011","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.canlet.2007.03.022","article-title":"The cancer preventive peptide lunasin from wheat inhibits core histone acetylation","volume":"255","author":"Jeong","year":"2007","journal-title":"Cancer Lett."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib31","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1002\/jsfa.8719","article-title":"Updating the research on the chemopreventive and therapeutic role of the peptide lunasin","volume":"98","author":"Hsieh","year":"2018","journal-title":"J. Sci. Food Agric."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118317_bib32","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.peptides.2008.11.002","article-title":"Lunasin, a novel seed peptide for cancer prevention","volume":"30","author":"Hern\u00e1ndez-Ledesma","year":"2009","journal-title":"Peptides"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib33","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.canlet.2009.12.019","article-title":"Lunasin peptide purified from Solanum nigrum L. protects DNA from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction","volume":"293","author":"Jeong","year":"2010","journal-title":"Cancer Lett."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib34","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.bbrc.2009.10.053","article-title":"Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages","volume":"390","author":"Hern\u00e1ndez-Ledesma","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib35","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","article-title":"INFOGEST static in vitro simulation of gastrointestinal food digestion","volume":"14","author":"Brodkorb","year":"2019","journal-title":"Nat. Protoc."},{"issue":"21","key":"10.1016\/j.ejmech.2025.118317_bib36","doi-asserted-by":"crossref","DOI":"10.1002\/mnfr.202000401","article-title":"Gastrointestinal digestion of food proteins under the effects of released bioactive peptides on digestive health","volume":"64","author":"Fern\u00e1ndez-Tom\u00e9","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.ejmech.2025.118317_bib37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jfca.2017.01.011","article-title":"Transepithelial transport of lunasin and derived peptides: inhibitory effects on the gastrointestinal cancer cells viability","volume":"68","author":"Fern\u00e1ndez-Tom\u00e9","year":"2018","journal-title":"J. Food Compos. Anal."},{"issue":"26","key":"10.1016\/j.ejmech.2025.118317_bib38","doi-asserted-by":"crossref","first-page":"10703","DOI":"10.1021\/jf072107c","article-title":"In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI","volume":"55","author":"Park","year":"2007","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008890","article-title":"Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable","volume":"5","author":"Hsieh","year":"2010","journal-title":"PLoS One"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib40","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1208\/s12248-015-9719-7","article-title":"Intranasal delivery of proteins and peptides in the treatment of neurodegenerative diseases","volume":"17","author":"Meredith","year":"2015","journal-title":"AAPS J."},{"issue":"7","key":"10.1016\/j.ejmech.2025.118317_bib41","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3390\/medicina55070393","article-title":"Intra-nasally administered oligopeptide lunasin acts as a possible anti-psychotic agent in mice models","volume":"55","author":"Dzirkale","year":"2019","journal-title":"Medicina (Kaunas)"},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib42","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.3390\/pharmaceutics14102214","article-title":"Liposomes loaded with amaranth unsaponifiable matter and soybean lunasin prevented melanoma tumor development overexpressing Caspase-3 in an in vivo model","volume":"14","author":"Casta\u00f1eda-Reyes","year":"2022","journal-title":"Pharmaceutics"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib43","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1021\/jf803303k","article-title":"Presence of lunasin in plasma of men after soy protein consumption","volume":"57","author":"Dia","year":"2009","journal-title":"J. Agric. Food Chem."},{"issue":"Pt B","key":"10.1016\/j.ejmech.2025.118317_bib44","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.phrs.2016.03.040","article-title":"Pharmacological research on natural substances in Latvia: focus on lunasin, betulin, polyprenol and phlorizin","volume":"113","author":"Muceniece","year":"2016","journal-title":"Pharmacol. Res."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118317_bib45","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1080\/01635580902850082","article-title":"The cancer preventive seed peptide lunasin from rye is bioavailable and bioactive","volume":"61","author":"Jeong","year":"2009","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.ejmech.2025.118317_bib46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.foodres.2016.10.051","article-title":"Kunitz trypsin inhibitor in addition to bowman-birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis","volume":"90","author":"Price","year":"2016","journal-title":"Food Res. Int."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib47","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.foodchem.2012.09.101","article-title":"Structural property of soybean lunasin and development of a method to quantify lunasin in plasma using an optimized immunoassay protocol","volume":"138","author":"Dia","year":"2013","journal-title":"Food Chem."},{"issue":"18","key":"10.1016\/j.ejmech.2025.118317_bib48","doi-asserted-by":"crossref","first-page":"12002","DOI":"10.1021\/acs.jmedchem.2c00539","article-title":"Discovery of cyclic peptide inhibitors targeting PD-L1 for cancer immunotherapy","volume":"65","author":"Fetse","year":"2022","journal-title":"J. Med. Chem."},{"issue":"7","key":"10.1016\/j.ejmech.2025.118317_bib49","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.tips.2023.04.003","article-title":"Recent advances in the development of therapeutic peptides","volume":"44","author":"Fetse","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2025.118317_bib50","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.biochi.2022.04.001","article-title":"Study on activation mechanism and cleavage sites of recombinant butelase-1 zymogen derived from Clitoria ternatea","volume":"199","author":"Zhao","year":"2022","journal-title":"Biochimie"},{"issue":"37","key":"10.1016\/j.ejmech.2025.118317_bib51","doi-asserted-by":"crossref","first-page":"23105","DOI":"10.1039\/D1RA03763C","article-title":"Characterization and application of natural and recombinant butelase-1 to improve industrial enzymes by end-to-end circularization","volume":"11","author":"Hemu","year":"2021","journal-title":"RSC Adv."},{"issue":"Pt 2","key":"10.1016\/j.ejmech.2025.118317_bib52","article-title":"\"Top-down\" overexpression optimization of butelase-1 in Escherichia coli and its application in anti-tumor peptides","volume":"276","author":"Zhao","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejmech.2025.118317_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2023.106892","article-title":"Backbone N-methylation of peptides: advances in synthesis and applications in pharmaceutical drug development","volume":"141","author":"Li","year":"2023","journal-title":"Bioorg. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib54","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nprot.2011.450","article-title":"Synthesis of N-methylated cyclic peptides","volume":"7","author":"Chatterjee","year":"2012","journal-title":"Nat. Protoc."},{"issue":"9","key":"10.1016\/j.ejmech.2025.118317_bib55","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2174\/1389557516666160322152457","article-title":"N-Methylated \u03b1-Amino acids and peptides: synthesis and biological activity","volume":"16","author":"Di Gioia","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib56","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1021\/acsinfecdis.9b00097","article-title":"N-Methylation of amino acids in gelatinase biosynthesis-activating pheromone identifies key site for stability enhancement with retention of the Enterococcus faecalis fsr quorum sensing circuit response","volume":"5","author":"McBrayer","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.ejmech.2025.118317_bib57","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jconrel.2020.09.055","article-title":"Peptide-functionalized liposomes as therapeutic and diagnostic tools for cancer treatment","volume":"329","author":"Sonju","year":"2021","journal-title":"J. Contr. Release"},{"issue":"12","key":"10.1016\/j.ejmech.2025.118317_bib58","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1021\/acs.biomac.9b01291","article-title":"Cancer nanomedicines based on synthetic polypeptides","volume":"20","author":"Sun","year":"2019","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.ejmech.2025.118317_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/j.plantsci.2021.110912","article-title":"Development of soybean experimental lines with enhanced protein and sulfur amino acid content","volume":"308","author":"Alaswad","year":"2021","journal-title":"Plant Sci."},{"issue":"3\u20134","key":"10.1016\/j.ejmech.2025.118317_bib60","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/21678421.2018.1556698","article-title":"Lunasin does not slow ALS progression: results of an open-label, single-center, hybrid-virtual 12-month trial","volume":"20","author":"Bedlack","year":"2019","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"46","key":"10.1016\/j.ejmech.2025.118317_bib61","doi-asserted-by":"crossref","first-page":"80826","DOI":"10.18632\/oncotarget.20590","article-title":"Lunasin functionally enhances LDL uptake via inhibiting PCSK9 and enhancing LDLR expression in vitro and in vivo","volume":"8","author":"Gu","year":"2017","journal-title":"Oncotarget"},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1080\/10826068.2017.1286600","article-title":"Hirudin as a novel fusion tag for efficient production of lunasin in Escherichia coli","volume":"47","author":"Tian","year":"2017","journal-title":"Prep. Biochem. Biotechnol."},{"issue":"12","key":"10.1016\/j.ejmech.2025.118317_bib63","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1039\/C7FO00992E","article-title":"Pepsin-pancreatin hydrolysis reduced the ability of lunasin-enriched material to inhibit activation of the inflammasomes in THP-1 human macrophages","volume":"8","author":"Price","year":"2017","journal-title":"Food Funct."},{"key":"10.1016\/j.ejmech.2025.118317_bib64","doi-asserted-by":"crossref","DOI":"10.29219\/fnr.v67.8991","article-title":"Seed-derived peptide lunasin suppressed breast cancer cell growth by regulating inflammatory mediators, aromatase, and estrogen receptors","volume":"67","author":"Hsieh","year":"2023","journal-title":"Food Nutr. Res."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118317_bib65","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.3390\/molecules24224140","article-title":"Lunasin improves the LDL-C lowering efficacy of simvastatin via inhibiting PCSK9 expression in hepatocytes and ApoE-\/- mice","volume":"24","author":"Gu","year":"2019","journal-title":"Molecules"},{"issue":"51","key":"10.1016\/j.ejmech.2025.118317_bib66","doi-asserted-by":"crossref","first-page":"84128","DOI":"10.18632\/oncotarget.11554","article-title":"Lunasin is a novel therapeutic agent for targeting melanoma cancer stem cells","volume":"7","author":"Shidal","year":"2016","journal-title":"Oncotarget"},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib67","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10555-010-9241-4","article-title":"The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells","volume":"29","author":"de Mejia","year":"2010","journal-title":"Cancer Metastasis Rev."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118317_bib68","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3390\/ijms21020537","article-title":"Inhibitory effects of peptide lunasin in colorectal cancer HCT-116 cells and their tumorsphere-derived subpopulation","volume":"21","author":"Fern\u00e1ndez-Tom\u00e9","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"18","key":"10.1016\/j.ejmech.2025.118317_bib69","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph191811678","article-title":"Liposomes containing amaranth unsaponifiable matter and soybean lunasin suppress ROS production in fibroblasts and reduced interleukin production in macrophages","volume":"19","author":"D\u00e1vila-Ortiz","year":"2022","journal-title":"Int. J. Environ. Res. Publ. Health"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib70","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib71","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/path.6261","article-title":"KAT8\/SIRT7-mediated Fascin-K41 acetylation\/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma","volume":"263","author":"Li","year":"2024","journal-title":"J. Pathol."},{"issue":"7","key":"10.1016\/j.ejmech.2025.118317_bib72","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/mnfr.201000632","article-title":"Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation","volume":"55","author":"Hern\u00e1ndez-Ledesma","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.ejmech.2025.118317_bib73","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.peptides.2016.09.006","article-title":"Lunasin is a redox sensitive intrinsically disordered peptide with two transiently populated \u03b1-helical regions","volume":"85","author":"Aleksis","year":"2016","journal-title":"Peptides"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-022-01259-6","article-title":"Targeting integrin pathways: mechanisms and advances in therapy","volume":"8","author":"Pang","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib75","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41573-021-00284-4","article-title":"Emerging therapeutic opportunities for integrin inhibitors","volume":"21","author":"Slack","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2025.118317_bib76","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.12688\/f1000research.9661.1","article-title":"Validation of syngeneic mouse models of melanoma and non-small cell lung cancer for investigating the anticancer effects of the soy-derived peptide lunasin","volume":"5","author":"Devapatla","year":"2016","journal-title":"F1000Res"},{"key":"10.1016\/j.ejmech.2025.118317_bib77","doi-asserted-by":"crossref","first-page":"902","DOI":"10.12688\/f1000research.55385.1","article-title":"The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1","volume":"10","author":"Kusmardi","year":"2021","journal-title":"F1000Res"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib78","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-79448-2","article-title":"Encapsulation of soybean lunasin and amaranth unsaponifiable matter in liposomes induces cell cycle arrest in an allograft melanoma mouse model","volume":"14","author":"Casta\u00f1eda-Reyes","year":"2024","journal-title":"Sci. Rep."},{"issue":"7","key":"10.1016\/j.ejmech.2025.118317_bib79","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41580-022-00456-z","article-title":"Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology","volume":"23","author":"Sies","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib80","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.ejmech.2025.118317_bib81","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodres.2019.108513","article-title":"Multifunctionality of lunasin and peptides released during its simulated gastrointestinal digestion","volume":"125","author":"Indiano-Romacho","year":"2019","journal-title":"Food Res. Int."},{"key":"10.1016\/j.ejmech.2025.118317_bib82","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.chroma.2014.10.019","article-title":"Off-line two dimensional isoelectrofocusing-liquid chromatography\/mass spectrometry (time of flight) for the determination of the bioactive peptide lunasin","volume":"1371","author":"Guijarro-D\u00edez","year":"2014","journal-title":"J. Chromatogr. A"},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib83","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth","volume":"41","author":"de Visser","year":"2023","journal-title":"Cancer Cell"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib84","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.immuni.2021.12.013","article-title":"Inflammation in obesity, diabetes, and related disorders","volume":"55","author":"Rohm","year":"2022","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib85","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1080\/21691401.2019.1623227","article-title":"Lunasin abrogates the expression of matrix metalloproteinases and reduction of type II collagen","volume":"47","author":"Dai","year":"2019","journal-title":"Artif. Cells, Nanomed. Biotechnol."},{"key":"10.1016\/j.ejmech.2025.118317_bib86","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2020.111908","article-title":"Seed peptide lunasin ameliorates obesity-induced inflammation and regulates immune responses in C57BL\/6J mice fed high-fat diet","volume":"147","author":"Hsieh","year":"2021","journal-title":"Food Chem. Toxicol."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118317_bib87","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0171969","article-title":"Lunasin attenuates obesity-related inflammation in RAW264.7 cells and 3T3-L1 adipocytes by inhibiting inflammatory cytokine production","volume":"12","author":"Hsieh","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"10.1016\/j.ejmech.2025.118317_bib88","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1016\/j.peptides.2009.08.005","article-title":"Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappaB pathway in the macrophage","volume":"30","author":"de Mejia","year":"2009","journal-title":"Peptides"},{"key":"10.1016\/j.ejmech.2025.118317_bib89","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/346839","article-title":"Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts","volume":"2015","author":"Jia","year":"2015","journal-title":"BioMed Res. Int."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib90","first-page":"56","article-title":"Characteristics of soybean (glycine max) protein hydrolysate by bromelain and its effect on inflammation and kidney disorders in gentamicin-induced Male Wistar rats","volume":"28","author":"Hidayat","year":"2025","journal-title":"Iran J Basic Med Sci"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib91","first-page":"84","article-title":"Lunazyna--peptyd o w\u0142a\u015bciwo\u015bciach przeciwnowotworowych [Lunasin--a novel chemopreventive peptide]","volume":"60","author":"Wo\u0142osik","year":"2014","journal-title":"Postepy Biochem."},{"issue":"8","key":"10.1016\/j.ejmech.2025.118317_bib92","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart disease and stroke Statistics-2023 update: a report from the American heart association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.ejmech.2025.118317_bib93","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105599","article-title":"Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis","volume":"168","author":"Duan","year":"2021","journal-title":"Pharmacol. Res."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118317_bib94","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/19390211.2019.1577937","article-title":"The effect of soybean lunasin on cardiometabolic risk factors: a randomized clinical trial","volume":"17","author":"Haddad","year":"2020","journal-title":"J. Diet. Suppl."},{"key":"10.1016\/j.ejmech.2025.118317_bib95","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.molimm.2017.09.004","article-title":"Lunasin abrogates monocytes to endothelial cells","volume":"92","author":"Zhu","year":"2017","journal-title":"Mol. Immunol."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib96","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-31787-7","article-title":"A soy protein Lunasin can ameliorate amyloid-beta 42 mediated neurodegeneration in drosophila eye","volume":"8","author":"Sarkar","year":"2018","journal-title":"Sci. Rep."},{"issue":"8","key":"10.1016\/j.ejmech.2025.118317_bib97","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.4103\/1673-5374.253509","article-title":"Exploring the efficacy of natural products in alleviating alzheimer's disease","volume":"14","author":"Deshpande","year":"2019","journal-title":"Neural Regen Res"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib98","doi-asserted-by":"crossref","first-page":"708","DOI":"10.4103\/1673-5374.353484","article-title":"Targeting neuroinflammation in Alzheimer's disease: from mechanisms to clinical applications","volume":"18","author":"Si","year":"2023","journal-title":"Neural Regen Res"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118317_bib99","first-page":"424","article-title":"Chemopreventive properties of Peptide Lunasin: a review","volume":"20","author":"Hern\u00e1ndez-Ledesma","year":"2013","journal-title":"Protein Pept. Lett."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118317_bib100","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s11033-024-10038-1","article-title":"TLR-4: a promising target for chemotherapy-induced peripheral neuropathy","volume":"51","author":"Babu","year":"2024","journal-title":"Mol. Biol. Rep."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib101","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1080\/14728222.2019.1676416","article-title":"Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders","volume":"23","author":"Leitner","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"issue":"19","key":"10.1016\/j.ejmech.2025.118317_bib102","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1007\/s00018-008-8064-8","article-title":"TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme","volume":"65","author":"Verstrepen","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118317_bib103","first-page":"154","article-title":"The effect of lunasin from Indonesian soybean extract on histopatologic examination and cox-2 expression in dextran sodium sulfate-induced mice colon","volume":"10","author":"Kusmardi","year":"2018","journal-title":"Int J Physiol Pathophysiol Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118317_bib104","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.fct.2013.12.021","article-title":"Antioxidant activity and protective effects of peptide lunasin against oxidative stress in intestinal Caco-2 cells","volume":"65","author":"Garc\u00eda-Nebot","year":"2014","journal-title":"Food Chem. Toxicol."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118317_bib105","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2025.118317_bib106","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155505","article-title":"A promising therapy for fatty liver disease: PCSK9 inhibitors","volume":"128","author":"Han","year":"2024","journal-title":"Phytomedicine"},{"issue":"2","key":"10.1016\/j.ejmech.2025.118317_bib107","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1159\/000479734","article-title":"Oral administration of CardioAid and lunasin alleviates liver damage in a high-fat diet Nonalcoholic Steatohepatitis model","volume":"96","author":"Drori","year":"2017","journal-title":"Digestion"},{"issue":"24","key":"10.1016\/j.ejmech.2025.118317_bib108","doi-asserted-by":"crossref","first-page":"9594","DOI":"10.3390\/ijms21249594","article-title":"Overexpression of soybean-derived lunasin in wheat and assessment of its anti-proliferative activity in colorectal cancer HT-29 cells","volume":"21","author":"Fan","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"15","key":"10.1016\/j.ejmech.2025.118317_bib109","doi-asserted-by":"crossref","first-page":"25525","DOI":"10.18632\/oncotarget.16066","article-title":"The soy-derived peptide Lunasin inhibits invasive potential of melanoma initiating cells","volume":"8","author":"Shidal","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejmech.2025.118317_bib110","doi-asserted-by":"crossref","DOI":"10.1016\/j.carbpol.2024.122145","article-title":"Chemical modification of hyaluronic acid as a strategy for the development of advanced drug delivery systems","volume":"337","author":"Bokatyi","year":"2024","journal-title":"Carbohydr. Polym."},{"issue":"20","key":"10.1016\/j.ejmech.2025.118317_bib111","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1021\/acs.jpcb.9b02368","article-title":"Chemical modification alters protein-protein interactions and can lead to lower protein solubility","volume":"123","author":"Quinn","year":"2019","journal-title":"J. Phys. Chem. B"},{"issue":"8","key":"10.1016\/j.ejmech.2025.118317_bib112","article-title":"Nanocarrier-Mediated photochemotherapy and photoradiotherapy","volume":"7","author":"Denkova","year":"2018","journal-title":"Adv. Healthcare Mater."},{"issue":"28","key":"10.1016\/j.ejmech.2025.118317_bib113","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202310531","article-title":"Lipid nanocarrier-based mRNA therapy: challenges and promise for clinical transformation","volume":"20","author":"Li","year":"2024","journal-title":"Small"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425010827?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425010827?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:01:58Z","timestamp":1780909318000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425010827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":113,"alternative-id":["S0223523425010827"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118317","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lunasin: Exploring the pharmacological potential of a soy-derived peptide","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118317","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"118317"}}