{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:13:43Z","timestamp":1792174423653,"version":"4.4.0"},"reference-count":182,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011360","name":"State Key Laboratory of Natural Medicines","doi-asserted-by":"publisher","award":["SKLNMKF202311"],"award-info":[{"award-number":["SKLNMKF202311"]}],"id":[{"id":"10.13039\/501100011360","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574254"],"award-info":[{"award-number":["82574254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273768"],"award-info":[{"award-number":["82273768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Advanced Research"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.jare.2026.05.030","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T22:59:12Z","timestamp":1779058752000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition revisited: advances and unmet challenges"],"prefix":"10.1016","author":[{"given":"Mengchen","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabing","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qidong","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziquan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-1582","authenticated-orcid":false,"given":"Zhengyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jare.2026.05.030_b0005","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1128\/MCB.15.8.4184","article-title":"Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins","volume":"15","author":"Itoh","year":"1995","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0010","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.jare.2026.05.030_b0015","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41573-025-01145-0","article-title":"Thirty years of NRF2: advances and therapeutic challenges","volume":"24","author":"Zhang","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0020","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0025","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1042\/BST20150049","article-title":"Keap1\/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism","volume":"43","author":"Chartoumpekis","year":"2015","journal-title":"Biochem Soc Trans"},{"key":"10.1016\/j.jare.2026.05.030_b0030","doi-asserted-by":"crossref","first-page":"8786","DOI":"10.1128\/MCB.23.23.8786-8794.2003","article-title":"Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway","volume":"23","author":"Kwak","year":"2003","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0035","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1128\/MCB.00248-10","article-title":"A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62","volume":"30","author":"Lau","year":"2010","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0040","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tibs.2008.12.008","article-title":"NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer","volume":"34","author":"Hayes","year":"2009","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0045","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tips.2013.04.005","article-title":"Toward clinical application of the Keap1\u2013Nrf2 pathway","volume":"34","author":"Suzuki","year":"2013","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0050","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1038\/s41388-025-03560-4","article-title":"NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting","volume":"44","author":"Panda","year":"2025","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2026.05.030_b0055","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.molmed.2016.05.002","article-title":"The dual roles of NRF2 in cancer","volume":"22","author":"Menegon","year":"2016","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0060","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.lungcan.2021.02.010","article-title":"Survival analysis for non-squamous NSCLC patients harbored STK11 or KEAP1 mutation receiving atezolizumab","volume":"154","author":"Shang","year":"2021","journal-title":"Lung Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0065","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1158\/1078-0432.CCR-19-1237","article-title":"Role of KEAP1\/NFE2L2 mutations in the chemotherapeutic response of patients with non-small cell lung cancer","volume":"26","author":"Jeong","year":"2020","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0070","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1093\/carcin\/bgp100","article-title":"Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice","volume":"30","author":"Yates","year":"2009","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.jare.2026.05.030_b0075","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibs.2014.02.002","article-title":"The Nrf2 regulatory network provides an interface between redox and intermediary metabolism","volume":"39","author":"Hayes","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0080","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ccr.2012.05.016","article-title":"Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming","volume":"22","author":"Mitsuishi","year":"2012","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0085","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/toxsci\/kfr183","article-title":"Beneficial role of Nrf2 in regulating NADPH generation and consumption","volume":"123","author":"Wu","year":"2011","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0090","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.jprot.2010.03.018","article-title":"Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver","volume":"73","author":"Kitteringham","year":"2010","journal-title":"J Proteomics"},{"key":"10.1016\/j.jare.2026.05.030_b0095","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.taap.2009.03.005","article-title":"Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents","volume":"237","author":"Higgins","year":"2009","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1016\/j.jare.2026.05.030_b0100","first-page":"95","article-title":"Regulation of glutathione synthesis","volume":"36","author":"Lu","year":"2000","journal-title":"Curr Top Cell Regul"},{"key":"10.1016\/j.jare.2026.05.030_b0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2025.103653","article-title":"Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression","volume":"83","author":"Sherwood","year":"2025","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0110","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.jare.2026.05.030_b0115","doi-asserted-by":"crossref","first-page":"26071","DOI":"10.1074\/jbc.274.37.26071","article-title":"Nrf2, a Cap\u2019n\u2019Collar transcription factor, regulates induction of the heme oxygenase-1 gene","volume":"274","author":"Alam","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0120","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41420-022-01117-y","article-title":"Interplay of Nrf2 and BACH1 in inducing ferroportin expression and enhancing resistance of human macrophages towards ferroptosis","volume":"8","author":"Namgaladze","year":"2022","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0125","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101243","article-title":"Non-canonical NRF2 activation promotes a pro-diabetic shift in hepatic glucose metabolism","volume":"51","author":"Liu","year":"2021","journal-title":"Mol Metab"},{"key":"10.1016\/j.jare.2026.05.030_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2023.102624","article-title":"Contribution of NRF2 to sulfur metabolism and mitochondrial activity","volume":"60","author":"Alam","year":"2023","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0135","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1128\/MCB.00915-07","article-title":"NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis","volume":"27","author":"Shin","year":"2007","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0140","doi-asserted-by":"crossref","first-page":"7416","DOI":"10.1093\/nar\/gks409","article-title":"Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha","volume":"40","author":"Chorley","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jare.2026.05.030_b0145","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1093\/nar\/gkq212","article-title":"Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis","volume":"38","author":"Malhotra","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jare.2026.05.030_b0150","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0155","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1812125115","article-title":"RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression","volume":"115","author":"Liu","year":"2018","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0160","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00395-011-0170-3","article-title":"Arterial flow reduces oxidative stress via an antioxidant response element and Oct-1 binding site within the NADPH oxidase 4 promoter in endothelial cells","volume":"106","author":"Goettsch","year":"2011","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.jare.2026.05.030_b0165","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s42003-020-01227-2","article-title":"Nrf2 contributes to the weight gain of mice during space travel","volume":"3","author":"Suzuki","year":"2020","journal-title":"Commun Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0170","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s42003-021-02334-4","article-title":"Nuclear factor E2-related factor 2 (NRF2) deficiency accelerates fast fibre type transition in soleus muscle during space flight","volume":"4","author":"Hayashi","year":"2021","journal-title":"Commun Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0175","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s42003-021-02904-6","article-title":"Nrf2 plays a critical role in the metabolic response during and after spaceflight","volume":"4","author":"Uruno","year":"2021","journal-title":"Commun Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0180","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.kint.2021.09.031","article-title":"Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel","volume":"101","author":"Suzuki","year":"2022","journal-title":"Kidney Int"},{"key":"10.1016\/j.jare.2026.05.030_b0185","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s42003-023-05251-w","article-title":"Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice","volume":"6","author":"Shimizu","year":"2023","journal-title":"Commun Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0190","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1089\/ars.2010.3222","article-title":"Discovery of the negative regulator of Nrf2, Keap1: a historical overview","volume":"13","author":"Itoh","year":"2010","journal-title":"Antioxid Redox Signal"},{"key":"10.1016\/j.jare.2026.05.030_b0195","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","article-title":"Direct interaction between Nrf2 and p21(Cip1\/WAF1) upregulates the Nrf2-mediated antioxidant response","volume":"34","author":"Chen","year":"2009","journal-title":"Mol Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0200","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1128\/MCB.25.24.10895-10906.2005","article-title":"The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation","volume":"25","author":"Nioi","year":"2005","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0205","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1128\/MCB.01639-08","article-title":"Acetylation of Nrf2 by p300\/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response","volume":"29","author":"Sun","year":"2009","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0210","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/onc.2012.59","article-title":"The nuclear cofactor RAC3\/AIB1\/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains","volume":"32","author":"Kim","year":"2013","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2026.05.030_b0215","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/MCB.00785-15","article-title":"The mediator subunit MED16 transduces NRF2-activating signals into antioxidant gene expression","volume":"36","author":"Sekine","year":"2016","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0220","doi-asserted-by":"crossref","first-page":"7942","DOI":"10.1128\/MCB.00700-06","article-title":"BRG1 interacts with Nrf2 to selectively mediate HO-1 induction in response to oxidative stress","volume":"26","author":"Zhang","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0225","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1038\/s41467-024-48364-4","article-title":"PPIA dictates NRF2 stability to promote lung cancer progression","volume":"15","author":"Lu","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0230","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/BST20150011","article-title":"Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of beta-TrCP and GSK-3","volume":"43","author":"Hayes","year":"2015","journal-title":"Biochem Soc Trans"},{"key":"10.1016\/j.jare.2026.05.030_b0235","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.freeradbiomed.2015.04.029","article-title":"Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3\/beta-TrCP","volume":"88","author":"Cuadrado","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0240","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/0008-5472.CAN-12-3386","article-title":"RXRalpha inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2","volume":"73","author":"Wang","year":"2013","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0245","doi-asserted-by":"crossref","first-page":"e1183","DOI":"10.1038\/cddis.2014.149","article-title":"Epigenetic modification of Nrf2 in 5-fluorouracil-resistant colon cancer cells: involvement of TET-dependent DNA demethylation","volume":"5","author":"Kang","year":"2014","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.jare.2026.05.030_b0250","doi-asserted-by":"crossref","first-page":"7066","DOI":"10.1038\/ncomms8066","article-title":"Neuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2","volume":"6","author":"Bell","year":"2015","journal-title":"Nat Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0255","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature10189","article-title":"Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis","volume":"475","author":"DeNicola","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.jare.2026.05.030_b0260","doi-asserted-by":"crossref","first-page":"20340","DOI":"10.1074\/jbc.M412081200","article-title":"Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes","volume":"280","author":"Miao","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0265","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/nar\/gkp1048","article-title":"An internal ribosomal entry site mediates redox-sensitive translation of Nrf2","volume":"38","author":"Li","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jare.2026.05.030_b0270","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1128\/MCB.00122-16","article-title":"G-Quadruplex in the NRF2 mRNA 5' untranslated region regulates De Novo NRF2 protein translation under oxidative stress","volume":"37","author":"Lee","year":"2017","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0275","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1074\/jbc.M207293200","article-title":"Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome","volume":"278","author":"Nguyen","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0280","doi-asserted-by":"crossref","first-page":"21592","DOI":"10.1074\/jbc.M300931200","article-title":"Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression","volume":"278","author":"McMahon","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0285","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.tibs.2024.12.010","article-title":"Regulating Nrf2 activity: ubiquitin ligases and signaling molecules in redox homeostasis","volume":"50","author":"Hayes","year":"2025","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0290","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\u2013protein interaction inhibitors: achievements, challenges, and future directions","volume":"59","author":"Jiang","year":"2016","journal-title":"J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0295","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.jare.2026.05.030_b0300","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1515\/BC.2006.164","article-title":"Two-site substrate recognition model for the Keap1-Nrf2 system: a hinge and latch mechanism","volume":"387","author":"Tong","year":"2006","journal-title":"Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0305","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 model","volume":"26","author":"Tong","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0310","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1073\/pnas.0914036107","article-title":"Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains","volume":"107","author":"Ogura","year":"2010","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0315","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1016\/j.apsb.2025.05.025","article-title":"Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis","volume":"15","author":"Yan","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.jare.2026.05.030_b0320","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.chembiol.2023.12.005","article-title":"Bivalent inhibitors of the BTB E3 ligase KEAP1 enable instant NRF2 activation to suppress acute inflammatory response","volume":"31","author":"Lu","year":"2023","journal-title":"Cell Chem Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0325","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.abb.2016.08.005","article-title":"Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants","volume":"617","author":"Dinkova-Kostova","year":"2017","journal-title":"Arch Biochem Biophys"},{"key":"10.1016\/j.jare.2026.05.030_b0330","doi-asserted-by":"crossref","first-page":"15259","DOI":"10.1073\/pnas.1305687110","article-title":"Regulatory flexibility in the Nrf2-mediated stress response is conferred by conformational cycling of the Keap1-Nrf2 protein complex","volume":"110","author":"Baird","year":"2013","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0335","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.biotechadv.2014.03.004","article-title":"Monitoring Keap1-Nrf2 interactions in single live cells","volume":"32","author":"Baird","year":"2014","journal-title":"Biotechnol Adv"},{"key":"10.1016\/j.jare.2026.05.030_b0340","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1128\/MCB.01204-10","article-title":"SCF\/{beta}-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner","volume":"31","author":"Rada","year":"2011","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0345","doi-asserted-by":"crossref","first-page":"31556","DOI":"10.1074\/jbc.M403061200","article-title":"Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron","volume":"279","author":"McMahon","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0350","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1038\/onc.2012.388","article-title":"Nrf2 is controlled by two distinct beta-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity","volume":"32","author":"Chowdhry","year":"2013","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2026.05.030_b0355","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.freeradbiomed.2021.03.034","article-title":"Regulation of Nrf2 by phosphorylation: consequences for biological function and therapeutic implications","volume":"168","author":"Liu","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0360","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1128\/MCB.00180-12","article-title":"Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3\/beta-TrCP axis","volume":"32","author":"Rada","year":"2012","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0365","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2025.103593","article-title":"Keap1-independent Nrf2 regulation: a novel therapeutic target for treating kidney disease","volume":"82","author":"Zhang","year":"2025","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0370","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1006762","article-title":"WDR23 regulates NRF2 independently of KEAP1","volume":"13","author":"Lo","year":"2017","journal-title":"PLoS Genet"},{"key":"10.1016\/j.jare.2026.05.030_b0375","doi-asserted-by":"crossref","first-page":"11783","DOI":"10.1038\/s41598-019-48286-y","article-title":"Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates","volume":"9","author":"Spatola","year":"2019","journal-title":"Sci Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0380","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gad.238246.114","article-title":"Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis","volume":"28","author":"Wu","year":"2014","journal-title":"Genes Dev"},{"key":"10.1016\/j.jare.2026.05.030_b0385","doi-asserted-by":"crossref","first-page":"12338","DOI":"10.1073\/pnas.92.26.12338","article-title":"Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region","volume":"92","author":"Park","year":"1995","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0390","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.molcel.2013.08.003","article-title":"Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy","volume":"51","author":"Ichimura","year":"2013","journal-title":"Mol Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0395","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1073\/pnas.0700898104","article-title":"A genomic screen for activators of the antioxidant response element","volume":"104","author":"Liu","year":"2007","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0400","doi-asserted-by":"crossref","first-page":"22576","DOI":"10.1074\/jbc.M110.118976","article-title":"p62\/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription","volume":"285","author":"Jain","year":"2010","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0405","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13578-023-00978-9","article-title":"Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy","volume":"13","author":"Xia","year":"2023","journal-title":"Cell Biosci"},{"key":"10.1016\/j.jare.2026.05.030_b0410","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrc3278","article-title":"NRF2 and cancer: the good, the bad and the importance of context","volume":"12","author":"Sporn","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0415","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.molcel.2006.03.004","article-title":"The double-edged sword of Nrf2: subversion of redox homeostasis during the evolution of cancer","volume":"21","author":"Hayes","year":"2006","journal-title":"Mol Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0420","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1146\/annurev-pharmtox-010818-021856","article-title":"Modulating NRF2 in disease: timing is everything","volume":"59","author":"Dodson","year":"2019","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.jare.2026.05.030_b0425","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the hallmarks of cancer","volume":"34","author":"Rojo de la Vega","year":"2018","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0430","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.semcancer.2021.05.016","article-title":"The intricacies of NRF2 regulation in cancer","volume":"76","author":"Schmidlin","year":"2021","journal-title":"Semin Cancer Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0435","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1089\/ars.2010.3276","article-title":"Regulation of NF-E2-related factor 2 signaling for cancer chemoprevention: antioxidant coupled with antiinflammatory","volume":"13","author":"Hu","year":"2010","journal-title":"Antioxid Redox Signal"},{"key":"10.1016\/j.jare.2026.05.030_b0440","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/carcin\/bgp231","article-title":"Nrf2: friend or foe for chemoprevention?","volume":"31","author":"Kensler","year":"2010","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.jare.2026.05.030_b0445","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/s42003-025-08983-z","article-title":"Druggable genome CRISPR screening identifies the KEAP1\/NRF2 axis as a mediator of PD-L1 expression","volume":"8","author":"Seker-Polat","year":"2025","journal-title":"Commun Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0450","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/s41416-025-03162-7","article-title":"Systemic activation of NRF2 contributes to the therapeutic efficacy of clinically-approved KRAS-G12C anti-cancer drugs","volume":"133","author":"Baird","year":"2025","journal-title":"Br J Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0455","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1038\/s41467-026-71608-4","article-title":"Differential KEAP1\/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy","volume":"17","author":"Samarin","year":"2026","journal-title":"Nat Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0460","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1101\/gad.225680.113","article-title":"The emerging role of the Nrf2-Keap1 signaling pathway in cancer","volume":"27","author":"Jaramillo","year":"2013","journal-title":"Genes Dev"},{"key":"10.1016\/j.jare.2026.05.030_b0465","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116234","article-title":"Disrupting mitochondrial dynamics attenuates ferroptosis and chemotoxicity via upregulating NRF2-mediated FSP1 expression","volume":"44","author":"Ma","year":"2025","journal-title":"Cell Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0470","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2025.103711","article-title":"Radiation-induced upregulation of itaconate in macrophages promotes the radioresistance of non-small cell lung cancer by stabilizing NRF2 protein and suppressing immune response","volume":"85","author":"Che","year":"2025","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0475","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1158\/0008-5472.CAN-22-1903","article-title":"NFE2L2 mutations enhance radioresistance in head and neck cancer by modulating intratumoral myeloid cells","volume":"83","author":"Guan","year":"2023","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0480","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113295","article-title":"KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance","volume":"42","author":"Zavitsanou","year":"2023","journal-title":"Cell Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0485","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1158\/2159-8290.CD-20-0282","article-title":"KEAP1\/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition","volume":"10","author":"Binkley","year":"2020","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0490","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1089\/ars.2017.7356","article-title":"The regulation of NRF2 by nutrient responsive signaling and its role in anabolic cancer metabolism","volume":"29","author":"Lee","year":"2017","journal-title":"Antioxid Redox Signal"},{"key":"10.1016\/j.jare.2026.05.030_b0495","doi-asserted-by":"crossref","first-page":"4941","DOI":"10.1038\/s41388-018-0314-0","article-title":"Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy","volume":"37","author":"Zhu","year":"2018","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2026.05.030_b0500","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41586-025-09493-y","article-title":"Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours","volume":"646","author":"Hegde","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.jare.2026.05.030_b0505","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2015.06.021","article-title":"Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease","volume":"88","author":"Tebay","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0510","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1021\/acs.chemrestox.6b00319","article-title":"Aldo-keto reductase regulation by the Nrf2 system: implications for stress response, chemotherapy drug resistance, and carcinogenesis","volume":"30","author":"Penning","year":"2017","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.jare.2026.05.030_b0515","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1158\/0008-5472.CAN-04-3544","article-title":"Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols","volume":"65","author":"Arlt","year":"2005","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0520","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 cancer","volume":"21","author":"Padmanabhan","year":"2006","journal-title":"Mol Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0525","doi-asserted-by":"crossref","first-page":"e420","DOI":"10.1371\/journal.pmed.0030420","article-title":"Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer","volume":"3","author":"Singh","year":"2006","journal-title":"PLoS Med"},{"key":"10.1016\/j.jare.2026.05.030_b0530","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1158\/0008-5472.CAN-07-5003","article-title":"Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth","volume":"68","author":"Ohta","year":"2008","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0535","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/jso.21520","article-title":"Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer","volume":"101","author":"Takahashi","year":"2010","journal-title":"J Surg Oncol"},{"key":"10.1016\/j.jare.2026.05.030_b0540","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.freeradbiomed.2015.07.153","article-title":"Hypermethylation of the Keap1 gene inactivates its function, promotes Nrf2 nuclear accumulation, and is involved in arsenite-induced human keratinocyte transformation","volume":"89","author":"Wang","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0545","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bbrc.2008.06.004","article-title":"Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues","volume":"373","author":"Wang","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0550","doi-asserted-by":"crossref","first-page":"710","DOI":"10.4161\/epi.6.6.15773","article-title":"Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer","volume":"6","author":"Muscarella","year":"2011","journal-title":"Epigenetics"},{"key":"10.1016\/j.jare.2026.05.030_b0555","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1471-2407-12-66","article-title":"Methylation of the KEAP1 gene promoter region in human colorectal cancer","volume":"12","author":"Hanada","year":"2012","journal-title":"BMC Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0560","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ccell.2016.06.022","article-title":"High-throughput phenotyping of lung cancer somatic mutations","volume":"30","author":"Berger","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0565","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014; 511:543-50. DOI: 10.1038\/nature13385.","DOI":"10.1038\/nature13385"},{"key":"10.1016\/j.jare.2026.05.030_b0570","doi-asserted-by":"crossref","first-page":"13568","DOI":"10.1073\/pnas.0806268105","article-title":"Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy","volume":"105","author":"Shibata","year":"2008","journal-title":"PNAS"},{"issue":"371\u201385","key":"10.1016\/j.jare.2026.05.030_b0575","first-page":"e18","article-title":"Comprehensive characterization of cancer driver genes and mutations","volume":"173","author":"Bailey","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0580","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ccell.2020.06.001","article-title":"Oxidative stress in cancer","volume":"38","author":"Hayes","year":"2020","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jare.2026.05.030_b0585","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/1476-4598-12-124","article-title":"Frequent concerted genetic mechanisms disrupt multiple components of the NRF2 inhibitor KEAP1\/CUL3\/RBX1 E3-ubiquitin ligase complex in thyroid cancer","volume":"12","author":"Martinez","year":"2013","journal-title":"Mol Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0590","doi-asserted-by":"crossref","first-page":"G419","DOI":"10.1152\/ajpgi.00296.2019","article-title":"Keap1 deletion accelerates mutant K-ras\/p53-driven cholangiocarcinoma","volume":"318","author":"Nabeshima","year":"2020","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jare.2026.05.030_b0595","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1158\/0008-5472.CAN-22-3848","article-title":"Distinct Nrf2 signaling thresholds mediate lung tumor initiation and progression","volume":"83","author":"DeBlasi","year":"2023","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0600","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.freeradbiomed.2016.09.010","article-title":"An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy","volume":"99","author":"Zhu","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0605","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.1021\/acs.jmedchem.8b01121","article-title":"Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition: an emerging strategy in cancer therapy","volume":"62","author":"Jiang","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0610","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116822","article-title":"NRF2 inhibitors: recent progress, future design and therapeutic potential","volume":"279","author":"Lv","year":"2024","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0615","doi-asserted-by":"crossref","DOI":"10.1016\/j.apsb.2025.10.004","article-title":"m6A readers: Promising therapeutic targets in cancer treatment","author":"Wang","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.jare.2026.05.030_b0620","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s40265-016-0674-0","article-title":"Insulin resistance and neurodegeneration: progress towards the development of new therapeutics for Alzheimer's disease","volume":"77","author":"De la Monte","year":"2017","journal-title":"Drugs"},{"key":"10.1016\/j.jare.2026.05.030_b0625","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.freeradbiomed.2012.05.038","article-title":"An effective strategy for increasing the radiosensitivity of Human lung Cancer cells by blocking Nrf2-dependent antioxidant responses","volume":"53","author":"Lee","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0630","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1021\/acschembio.5b00448","article-title":"A small molecule inhibits deregulated NRF2 transcriptional activity in cancer","volume":"10","author":"Bollong","year":"2015","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0635","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1158\/1535-7163.MCT-21-0210","article-title":"A novel Nrf2 pathway inhibitor sensitizes keap1-mutant lung cancer cells to chemotherapy","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.jare.2026.05.030_b0640","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1039\/D2MD00211F","article-title":"Exploring structural effects in a new class of NRF2 inhibitors","volume":"14","author":"Hou","year":"2023","journal-title":"RSC Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0645","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1021\/acschembio.7b01025","article-title":"A complementary chemical and genomic screening approach for druggable targets in the Nrf2 pathway and small molecule inhibitors to overcome cancer cell drug resistance","volume":"13","author":"Matthews","year":"2018","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0650","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrd.2016.211","article-title":"Induced protein degradation: an emerging drug discovery paradigm","volume":"16","author":"Lai","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0655","doi-asserted-by":"crossref","first-page":"12030","DOI":"10.1038\/ncomms12030","article-title":"p62\/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming","volume":"7","author":"Saito","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0660","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2024.103117","article-title":"Inhibition of glycogen synthase kinase-3 enhances NRF2 protein stability, nuclear localisation and target gene transcription in pancreatic beta cells","volume":"71","author":"Patibandla","year":"2024","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0665","doi-asserted-by":"crossref","first-page":"17248","DOI":"10.1039\/D5SC04324G","article-title":"Discovery of an allosteric 14-3-3 inhibitor for suppressing NRF2-driven cancer via phenotypic screening and chemoproteomic-based target deconvolution","volume":"16","author":"Zhao","year":"2025","journal-title":"Chem Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0670","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1021\/acs.jmedchem.2c01909","article-title":"ARE-PROTACs enable Co-degradation of an Nrf2-MafG heterodimer","volume":"66","author":"Ji","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0675","article-title":"A covalent allosteric molecular glue suppresses NRF2-dependent cancer growth","author":"Roy","year":"2025","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0680","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113104","article-title":"A NRF2 inhibitor selectively sensitizes KEAP1 mutant tumor cells to cisplatin and gefitinib by restoring NRF2-inhibitory function of KEAP1 mutants","volume":"42","author":"Aboulkassim","year":"2023","journal-title":"Cell Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0685","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1158\/1535-7163.MCT-16-0332","article-title":"A novel polyphenol conjugate sensitizes cisplatin-resistant head and neck cancer cells to cisplatin via Nrf2 inhibition","volume":"15","author":"Kim","year":"2016","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.jare.2026.05.030_b0690","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.3390\/cancers14246120","article-title":"A new Nrf2 inhibitor enhances chemotherapeutic effects in glioblastoma cells carrying p53 mutations","volume":"14","author":"Afjei","year":"2022","journal-title":"Cancers"},{"key":"10.1016\/j.jare.2026.05.030_b0695","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41568-025-00817-8","article-title":"Targeted protein degradation for cancer therapy","volume":"25","author":"Hinterndorfer","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0700","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.apsb.2023.09.003","article-title":"Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies","volume":"14","author":"Peng","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.jare.2026.05.030_b0705","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1016\/j.apsb.2022.02.022","article-title":"Non-small molecule PROTACs (NSM-PROTACs): protein degradation kaleidoscope","volume":"12","author":"Ma","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.jare.2026.05.030_b0710","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2026.104009","article-title":"The electrophilic metabolite of kynurenine, kynurenine-CKA, targets C151 in Keap1 to derepress Nrf2","volume":"90","author":"Feng","year":"2026","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0715","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2025.103906","article-title":"KEAP1 C151 active site catalysis drives electrophilic signaling to upregulate cytoprotective enzyme expression","volume":"88","author":"Schnell","year":"2025","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0720","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2025.103885","article-title":"Bidirectional regulation of KEAP1 BTB domain-based sensor activity","volume":"87","author":"Suzuki","year":"2025","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0725","doi-asserted-by":"crossref","DOI":"10.1038\/s41589-026-02180-7","article-title":"Turning KEAP1 against NRF2","author":"Adamopoulos","year":"2026","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0730","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1021\/acschembio.6b00651","article-title":"Small molecule inhibitor of NRF2 selectively intervenes therapeutic resistance in KEAP1-deficient NSCLC tumors","volume":"11","author":"Singh","year":"2016","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0735","doi-asserted-by":"crossref","unstructured":"Alzufairi A A, Souilhol C, Jordan-Mahy N, Cross N A. Assessment of ferroptosis inducers and Nrf2 inhibitors as radiosensitisers in 2D and 3D breast cancer cell cultures. Cancer Biol 2023; bioRxiv DOI: 10.1101\/2023.12.08.570735.","DOI":"10.1101\/2023.12.08.570735"},{"key":"10.1016\/j.jare.2026.05.030_b0740","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2025.117912","article-title":"Discovery of novel thiazolylhydrazone derivatives as potent anti-cancer agents inducing ferroptosis via direct NRF2 inhibition","volume":"297","author":"Meng","year":"2025","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0745","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41420-024-01800-2","article-title":"Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway","volume":"10","author":"Yu","year":"2024","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.jare.2026.05.030_b0750","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113686","article-title":"Discovery and characterization of novel peptide inhibitors of the NRF2\/MAFG\/DNA ternary complex for the treatment of cancer","volume":"224","author":"Simov","year":"2021","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0755","doi-asserted-by":"crossref","first-page":"19589","DOI":"10.1073\/pnas.0709483104","article-title":"Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha","volume":"104","author":"Wang","year":"2007","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0760","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105516","article-title":"Cyclometalated Ru(II)-isoquinoline complexes overcome cisplatin resistance of A549\/DDP cells by downregulation of Nrf2 via Akt\/GSK-3\u03b2\/Fyn pathway","volume":"119","author":"Chen","year":"2022","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0765","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0267651","article-title":"Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions","volume":"17","author":"Wiedemann","year":"2022","journal-title":"PLoS One"},{"key":"10.1016\/j.jare.2026.05.030_b0770","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.1021\/acs.jmedchem.2c02037","article-title":"Stapled peptides as direct inhibitors of Nrf2-sMAF transcription factors","volume":"66","author":"Modi","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0775","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/bjc.2014.380","article-title":"Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells","volume":"111","author":"Valenzuela","year":"2014","journal-title":"Br J Cancer"},{"key":"10.1016\/j.jare.2026.05.030_b0780","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1073\/pnas.1014275108","article-title":"Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism","volume":"108","author":"Ren","year":"2011","journal-title":"PNAS"},{"key":"10.1016\/j.jare.2026.05.030_b0785","doi-asserted-by":"crossref","first-page":"7430","DOI":"10.1158\/0008-5472.CAN-14-1439","article-title":"Oncogenic KRAS confers chemoresistance by upregulating NRF2","volume":"74","author":"Tao","year":"2014","journal-title":"Cancer Res"},{"key":"10.1016\/j.jare.2026.05.030_b0790","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/mc.22745","article-title":"The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer","volume":"57","author":"Tao","year":"2018","journal-title":"Mol Carcinog"},{"key":"10.1016\/j.jare.2026.05.030_b0795","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1074\/mcp.M115.055509","article-title":"Application of mass spectrometry profiling to establish brusatol as an inhibitor of global protein synthesis","volume":"15","author":"Vartanian","year":"2015","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.jare.2026.05.030_b0800","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/mc.22609","article-title":"Brusatol overcomes chemoresistance through inhibition of protein translation","volume":"56","author":"Harder","year":"2017","journal-title":"Mol Carcinog"},{"key":"10.1016\/j.jare.2026.05.030_b0805","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/j.freeradbiomed.2011.03.008","article-title":"Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2\/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs","volume":"50","author":"Tang","year":"2011","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0810","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2014.04.039","article-title":"Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo","volume":"447","author":"Chian","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0815","first-page":"2179","article-title":"Luteolin induces mitochondrial apoptosis in HT29 cells by inhibiting the Nrf2\/ARE signaling pathway","volume":"19","author":"Yang","year":"2020","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.jare.2026.05.030_b0820","doi-asserted-by":"crossref","first-page":"37157","DOI":"10.1038\/srep37157","article-title":"Regulation of Sirt1\/Nrf2\/TNF-alpha signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity","volume":"6","author":"Yang","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0825","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.freeradbiomed.2014.03.009","article-title":"Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE pathway","volume":"71","author":"Xu","year":"2014","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0830","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.7150\/ijbs.82401","article-title":"Natural Nrf2 inhibitors: a review of their potential for cancer treatment","volume":"19","author":"Zhang","year":"2023","journal-title":"Int J Biol Sci"},{"key":"10.1016\/j.jare.2026.05.030_b0835","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1039\/C9NP00061E","article-title":"The role of natural products in revealing NRF2 function","volume":"37","author":"Zhang","year":"2020","journal-title":"Nat Prod Rep"},{"key":"10.1016\/j.jare.2026.05.030_b0840","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s42255-020-0191-z","article-title":"NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism","volume":"2","author":"Fox","year":"2020","journal-title":"Nat Metab"},{"issue":"487\u2013503","key":"10.1016\/j.jare.2026.05.030_b0845","first-page":"e7","article-title":"NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer","volume":"35","author":"Weiss-Sadan","year":"2023","journal-title":"Cell Metab"},{"key":"10.1016\/j.jare.2026.05.030_b0850","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.taap.2013.05.010","article-title":"Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways","volume":"271","author":"Do","year":"2013","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1016\/j.jare.2026.05.030_b0855","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2014.06.010","article-title":"Metformin induces microRNA-34a to downregulate the Sirt1\/Pgc-1alpha\/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents","volume":"74","author":"Do","year":"2014","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jare.2026.05.030_b0860","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.cmet.2016.09.006","article-title":"Environment dictates dependence on mitochondrial complex I for NAD+ and aspartate production and determines cancer cell sensitivity to metformin","volume":"24","author":"Gui","year":"2016","journal-title":"Cell Metab"},{"key":"10.1016\/j.jare.2026.05.030_b0865","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s11011-014-9632-2","article-title":"Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia","volume":"30","author":"Ashabi","year":"2015","journal-title":"Metab Brain Dis"},{"key":"10.1016\/j.jare.2026.05.030_b0870","doi-asserted-by":"crossref","first-page":"e00377","DOI":"10.1128\/MCB.00377-20","article-title":"Geldanamycin-derived HSP90 inhibitors are synthetic lethal with NRF2","volume":"40","author":"Baird","year":"2020","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0875","doi-asserted-by":"crossref","first-page":"e00473","DOI":"10.1128\/MCB.00473-20","article-title":"NRF2-dependent bioactivation of mitomycin c as a novel strategy to target KEAP1-NRF2 pathway activation in human cancer","volume":"41","author":"Baird","year":"2021","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jare.2026.05.030_b0880","doi-asserted-by":"crossref","first-page":"12543","DOI":"10.1093\/nar\/gkac1102","article-title":"Structural basis of transcription regulation by CNC family transcription factor, Nrf2","volume":"50","author":"Sengoku","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jare.2026.05.030_b0885","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.bbamcr.2014.05.003","article-title":"Modulation of NRF2 signaling pathway by nuclear receptors: implications for cancer","volume":"1843","author":"Namani","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jare.2026.05.030_b0890","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.bbrc.2014.08.111","article-title":"Rexinoid inhibits Nrf2-mediated transcription through retinoid X receptor alpha","volume":"452","author":"Wu","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.jare.2026.05.030_b0895","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mce.2007.08.011","article-title":"ERRbeta: a potent inhibitor of Nrf2 transcriptional activity","volume":"278","author":"Zhou","year":"2007","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.jare.2026.05.030_b0900","doi-asserted-by":"crossref","first-page":"50810","DOI":"10.1074\/jbc.M404984200","article-title":"Nrf3 negatively regulates antioxidant-response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene","volume":"279","author":"Sankaranarayanan","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2026.05.030_b0905","doi-asserted-by":"crossref","first-page":"16891","DOI":"10.1074\/jbc.M500166200","article-title":"Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants","volume":"280","author":"Dhakshinamoorthy","year":"2005","journal-title":"J Biol Chem"},{"issue":"316\u201329","key":"10.1016\/j.jare.2026.05.030_b0910","first-page":"e18","article-title":"Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of bach1","volume":"178","author":"Lignitto","year":"2019","journal-title":"Cell"}],"container-title":["Journal of Advanced Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S209012322600425X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S209012322600425X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:02:13Z","timestamp":1783130533000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S209012322600425X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":182,"alternative-id":["S209012322600425X"],"URL":"https:\/\/doi.org\/10.1016\/j.jare.2026.05.030","relation":{},"ISSN":["2090-1232"],"issn-type":[{"value":"2090-1232","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition revisited: advances and unmet challenges","name":"articletitle","label":"Article Title"},{"value":"Journal of Advanced Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jare.2026.05.030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V. on behalf of Cairo University.","name":"copyright","label":"Copyright"}]}}