{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:21:14Z","timestamp":1793089274191,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"21","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry"],"published-print":{"date-parts":[[2020,11]]},"DOI":"10.1016\/j.bmc.2020.115738","type":"journal-article","created":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T14:00:35Z","timestamp":1598796035000},"page":"115738","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction"],"prefix":"10.1016","volume":"28","author":[{"given":"Stefania","family":"Colarusso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"De Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Frattarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Andreini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Cerretani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Missineo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tambone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Kempf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Augustin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Steinbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Munoz-Sanjuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Summa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Tomei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bresciani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Toledo-Sherman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2020.115738_h0005","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12551-016-0244-4","article-title":"The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases","volume":"9","author":"Deshmukh","year":"2017","journal-title":"Biophys Rev"},{"key":"10.1016\/j.bmc.2020.115738_h0010","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/med.21396","article-title":"The KEAP1\u2013NRF2\u2013ARE pathway as a potential preventive and therapeutic target: an update","volume":"36","author":"Lu","year":"2016","journal-title":"Med Res Rev"},{"issue":"part B","key":"10.1016\/j.bmc.2020.115738_h0015","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.freeradbiomed.2015.07.147","article-title":"A. NRF2-a therapeutic target for the treatment of neurodegenerative diseases","volume":"88","author":"Johnson","year":"2015","journal-title":"Free Radical Biol Med"},{"key":"10.1016\/j.bmc.2020.115738_h0020","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1471-2199-9-84","article-title":"Mutant Huntingtin activates NRF2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease","volume":"9","author":"Van Roon-Mom","year":"2008","journal-title":"BMC Mol Biol"},{"key":"10.1016\/j.bmc.2020.115738_h0025","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An NRF2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.bmc.2020.115738_h0030","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00204-011-0674-5","article-title":"The cytoprotective role of the KEAP1-NRF2 pathway","volume":"85","author":"Baird","year":"2011","journal-title":"Arch Toxicol"},{"key":"10.1016\/j.bmc.2020.115738_h0035","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1073\/pnas.94.10.5361","article-title":"Functional antioxidant responsive elements","volume":"94","author":"Wasserman","year":"1997","journal-title":"Proc Nat Acad Sci"},{"key":"10.1016\/j.bmc.2020.115738_h0040","doi-asserted-by":"crossref","first-page":"54750","DOI":"10.1074\/jbc.M410073200","article-title":"Crystal structure of the Kelch domain of human Keap1","volume":"279","author":"Li","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bmc.2020.115738_h0045","doi-asserted-by":"crossref","first-page":"10941","DOI":"10.1128\/MCB.24.24.10941-10953.2004","article-title":"Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex","volume":"24","author":"Zhang","year":"2004","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.bmc.2020.115738_h0050","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1128\/MCB.26.8.2887-2900.2006","article-title":"Keap1 recruits Neh2 through binding to ETGE and DLG Motifs: characterization of the two-site molecular recognition mode","volume":"26","author":"Tong","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.bmc.2020.115738_h0055","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1046\/j.1365-2443.2003.00640.x","article-title":"Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles","volume":"8","author":"Itoh","year":"2003","journal-title":"Genes Cells"},{"key":"10.1016\/j.bmc.2020.115738_h0060","doi-asserted-by":"crossref","first-page":"10837","DOI":"10.1021\/acs.jmedchem.6b00586","article-title":"Discovery and development of Kelch-like ECH-associated protein 1: nuclear factor Erythroid 2-related factor 2 (KEAP1:NRF2) protein-protein interaction inhibitors: achievements, challenges and future directions","volume":"59","author":"Jiang","year":"2016","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_h0065","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1021\/acs.jmedchem.6b00228","article-title":"Monoacidic inhibitors of the Kelch-like ECH-associated protein 1: nuclear factor erythroid 2-related factor 2 (KEAP1:NRF2) protein-protein interaction with high cell potency identified by fragment-based","volume":"59","author":"Davies","year":"2016","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_b0025","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.freeradbiomed.2015.05.034","article-title":"Structural basis of KEAP1 interactions with NRF2","volume":"88","author":"Canning","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.bmc.2020.115738_h0075","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.molcel.2006.01.013","article-title":"Structural basis for defects of keap1 activity provoked by its point mutations in lung","volume":"21","author":"Padmanabhan","year":"2006","journal-title":"Mol Cell"},{"key":"10.1016\/j.bmc.2020.115738_h0080","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1038\/sj.emboj.7601243","article-title":"Structure of the KEAP1:NRF2 interface provides mechanistic insight into NRF2 signaling","volume":"25","author":"Lo","year":"2006","journal-title":"Embo J"},{"key":"10.1016\/j.bmc.2020.115738_b0035","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/cmdc.201300525","article-title":"Binding mode and structure-activity relationships around direct inhibitors of the NRF2-KEAP1 complex","volume":"9","author":"Jnoff","year":"2014","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bmc.2020.115738_b0040","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ejmech.2015.08.049","article-title":"Probing the structural requirements of non-electrophilic naphthalene-based NRF2 activators","volume":"103","author":"Jain","year":"2015","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_h0095","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ddtec.2017.10.001","article-title":"The KEAP1\u2013NRF2 protein\u2013protein interaction: a suitable target for small molecules","author":"Schmoll","year":"2017","journal-title":"Drug Discov Today: Technol"},{"issue":"18","key":"10.1016\/j.bmc.2020.115738_h0100","doi-asserted-by":"crossref","first-page":"8088","DOI":"10.1021\/acs.jmedchem.8b00358","article-title":"Non-covalent small-molecule Kelch-like ECH-associated protein 1\u2013nuclear factor Erythroid 2-related factor 2 (Keap1\u2013Nrf2) inhibitors and their potential for targeting central nervous system diseases","volume":"61","author":"Pallesen","year":"2018","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_h0105","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.freeradbiomed.2011.10.486","article-title":"Peptide inhibitors of the KEAP1\u2013NRF2 protein\u2013protein interaction","volume":"52","author":"Hancock","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.bmc.2020.115738_h0110","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1039\/c3ob40249e","article-title":"Peptide inhibitors of the KEAP1\u2013NRF2 protein\u2013protein interaction with improved binding and cellular activity","volume":"11","author":"Hancock","year":"2013","journal-title":"Org Biomol Chem"},{"issue":"6","key":"10.1016\/j.bmc.2020.115738_h0115","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1021\/jm5000529","article-title":"Discovery of potent Keap1\u2013Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis","volume":"57","author":"Jiang","year":"2014","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_h0120","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1002\/cbic.201800170","article-title":"Modified peptide inhibitors of the Keap1\u2013Nrf2 protein-protein interaction incorporating unnatural amino acids","volume":"19","author":"Georgakopoulos","year":"2018","journal-title":"ChemBioChem"},{"key":"10.1016\/j.bmc.2020.115738_b0055","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cbpa.2017.02.006","article-title":"Cyclic peptide therapeutics: past, present and future","volume":"38","author":"Zorzi","year":"2017","journal-title":"Curr Opin Chem Biol"},{"key":"10.1016\/j.bmc.2020.115738_h0130","first-page":"592","article-title":"Crystal-contact engineering to obtain a crystal form of the Kelch domain of human KEAP1 suitable for ligand-soaking experiments","volume":"F69","author":"Hoerer","year":"2013","journal-title":"Acta Cryst"},{"key":"10.1016\/j.bmc.2020.115738_h0135","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.ejmech.2017.10.052","volume":"143","author":"Lu","year":"2018","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_b0065","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1039\/C4MD00131A","article-title":"Towards understanding cell penetration by stapled peptides","volume":"6","author":"Chu","year":"2015","journal-title":"Med Chem Commun"},{"key":"10.1016\/j.bmc.2020.115738_b0070","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1021\/ml300041g","article-title":"Anti-inflammatory effect of a cell-penetrating peptide targeting the NRF2\/KEAP1 interaction","volume":"3","author":"Steel","year":"2012","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmc.2020.115738_b0075","first-page":"4900","article-title":"The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novelactivatable forms of Xentry","volume":"4","author":"Montrose","year":"2014","journal-title":"Nat Sci Rep"},{"key":"10.1016\/j.bmc.2020.115738_b0080","doi-asserted-by":"crossref","first-page":"8995","DOI":"10.1021\/ja2017416","article-title":"Spontaneous membrane-translocating peptides by orthogonal high-throughput screening","volume":"133","author":"Marks","year":"2011","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.bmc.2020.115738_b0085","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/nar\/gkg160","article-title":"Cellular uptake of Antennapedia Penetratin peptides is a two-step process in which phase transfer precedes a tryptophan-dependent translocation","volume":"31","author":"Dom","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.bmc.2020.115738_b0090","doi-asserted-by":"crossref","first-page":"11719","DOI":"10.1038\/srep11719","article-title":"Discovery of a non-cationic cell penetrating peptide derived from membrane-interacting human proteins and its potential as a protein delivery carrier","volume":"5","author":"Kim","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.bmc.2020.115738_h0170","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2017.08.003","article-title":"Nuclear factor (erythroid-derived 2)-like 2 (NRF2) drug discovery: Biochemical toolbox to develop NRF2 activators by reversible binding of Kelch-like ECH-associated protein 1 (KEAP1)","volume":"631","author":"Bresciani","year":"2017","journal-title":"Arch Biochem Biophys"},{"key":"10.1016\/j.bmc.2020.115738_h0175","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chembiol.2011.03.013","article-title":"Development of Neh2-luciferase reporter and its application for high throughput screening and real-time monitoring of NRF2 activators","volume":"18","author":"Smirnova","year":"2011","journal-title":"Chem Biol"},{"key":"10.1016\/j.bmc.2020.115738_b0100","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1038\/sj.emboj.7601243","article-title":"Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling","volume":"25","author":"Lo","year":"2006","journal-title":"EMBO J"},{"key":"10.1016\/j.bmc.2020.115738_b0105","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_b0110","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_b0115","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2020.115738_b0120","unstructured":"PyMOL(TM) Molecular Graphics System, Version 1.8.4.0. Copyright (c) Schrodinger, LLC."},{"key":"10.1016\/j.bmc.2020.115738_b0125","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1021\/acsmedchemlett.9b00594","article-title":"Combined peptide and small-molecule approach towards non-acidic THIQ inhibitors of the KEAP1\/NRF2 interaction","volume":"11","author":"Ontoria","year":"2020","journal-title":"ACS Med Chem Lett"}],"container-title":["Bioorganic & Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096808962030568X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096808962030568X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:08:52Z","timestamp":1760836132000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S096808962030568X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":41,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["S096808962030568X"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2020.115738","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2020.115738","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115738"}}