{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:38:36Z","timestamp":1786743516135,"version":"build-2736575974"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26460098"],"award-info":[{"award-number":["JP26460098"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K08309"],"award-info":[{"award-number":["JP17K08309"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H03379"],"award-info":[{"award-number":["JP19H03379"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alport Syndrome Research Funding Program of the Alport Syndrome Foundation"},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Grant-in-Aid for JSPS Fellows for Young Researchers","award":["JP19J23608"],"award-info":[{"award-number":["JP19J23608"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ek0310017"],"award-info":[{"award-number":["JP21ek0310017"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2022,4,28]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bardoxolone methyl activates nuclear factor erythroid 2\u2013related factor 2 (Nrf2)\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      covalent binding and irreversible inhibition of Kelch-like ECH-associated protein 1 (Keap1), the negative regulator of Nrf2. Ongoing clinical trials of bardoxolone methyl show promising effects for patients with CKD. However, the direct inhibition of Keap1-Nrf2 protein-protein interaction (PPI) as an approach to activate Nrf2 is less explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed a noncovalent Nrf2 activator UBE-1099, which highly selectively inhibits Keap1-Nrf2 PPI, and evaluated its efficacy on the progressive phenotype in an Alport syndrome mouse model (\n                      <jats:italic toggle=\"yes\">Col4a5<\/jats:italic>\n                      -G5X).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Similar to bardoxolone methyl, UBE-1099 transiently increased proteinuria and reduced plasma creatinine in Alport mice. Importantly, UBE-1099 improved the glomerulosclerosis, renal inflammation, and fibrosis, and prolonged the life span of Alport mice. UBE-1099 ameliorated the dysfunction of Nrf2 signaling in the renal tissue of Alport mice. Moreover, transcriptome analysis in the glomerulus showed that UBE-1099 induced the expression of genes associated with the cell cycle and cytoskeleton, which may explain its unique mechanism of improvement such as glomerular morphologic change.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>UBE-1099 significantly ameliorates the progressive phenotype in Alport mice. Our results revealed the efficacy of Keap1-Nrf2 PPI inhibitor for glomerulosclerosis and present a potential therapeutic drug for CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0004572021","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T12:30:42Z","timestamp":1638534642000},"page":"687-699","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor UBE-1099 Ameliorates Progressive Phenotype in Alport Syndrome Mouse Model"],"prefix":"10.34067","volume":"3","author":[{"given":"Shota","family":"Kaseda","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Program for Leading Graduate School \u201cHIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,\u201d Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Sannomiya","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Horizono","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-0808","authenticated-orcid":false,"given":"Jun","family":"Kuwazuru","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6751-8352","authenticated-orcid":false,"given":"Mary Ann","family":"Suico","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Global Center for Natural Resources Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Ogi","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Sunamoto","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Fukiya","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Kamura","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Program for Leading Graduate School \u201cHIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,\u201d Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Niinou","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuimi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Nara","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Shuto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Global Center for Natural Resources Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Onuma","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Research Laboratory, UBE Industries Ltd., Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-2424","authenticated-orcid":false,"given":"Hirofumi","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Program for Leading Graduate School \u201cHIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,\u201d Kumamoto University, Kumamoto, Japan"},{"name":"Global Center for Natural Resources Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"B1-20250825","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"},{"issue":"Pt B","key":"B2-20250825","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":"B3-20250825","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.redox.2012.10.001","article-title":"The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer","volume":"1","author":"Kansanen","year":"2013","journal-title":"Redox Biol"},{"issue":"Pt B","key":"B4-20250825","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":"B5-20250825","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":"Proc Natl Acad Sci U S A"},{"key":"B6-20250825","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":"B7-20250825","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":"B8-20250825","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/med.21257","article-title":"Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents","volume":"32","author":"Magesh","year":"2012","journal-title":"Med Res Rev"},{"key":"B9-20250825","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa1105351","article-title":"Bardoxolone methyl and kidney function in CKD with type 2 diabetes","volume":"365","author":"Pergola","year":"2011","journal-title":"N Engl J Med"},{"key":"B10-20250825","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.ekir.2020.03.030","article-title":"Randomized clinical trial on the effect of bardoxolone methyl on GFR in diabetic kidney disease patients (TSUBAKI Study)","volume":"5","author":"Nangaku","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B11-20250825","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"Bardoxolone methyl in type 2 diabetes and Stage 4 chronic kidney disease","volume":"369","author":"de Zeeuw","year":"2013","journal-title":"N Engl J Med"},{"key":"B12-20250825","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1159\/000362906","article-title":"Mechanisms contributing to adverse cardiovascular events in patients with type 2 diabetes mellitus and Stage 4 chronic kidney disease treated with bardoxolone methyl","volume":"39","author":"Chin","year":"2014","journal-title":"Am J Nephrol"},{"key":"B13-20250825","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.taap.2018.09.030","article-title":"Nrf2 activator for the treatment of kidney diseases","volume":"360","author":"Yamawaki","year":"2018","journal-title":"Toxicol Appl Pharmacol"},{"key":"B14-20250825","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":"B15-20250825","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-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) inhibitors and their potential for targeting central nervous system diseases","volume":"61","author":"Pallesen","year":"2018","journal-title":"J Med Chem"},{"key":"B16-20250825","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.kint.2020.07.036","article-title":"Genetic or pharmacologic Nrf2 activation increases proteinuria in chronic kidney disease in mice","volume":"99","author":"Rush","year":"2021","journal-title":"Kidney Int"},{"key":"B17-20250825","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/ki.2012.393","article-title":"The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells","volume":"83","author":"Ding","year":"2013","journal-title":"Kidney Int"},{"key":"B18-20250825","doi-asserted-by":"crossref","first-page":"101266","DOI":"10.1016\/j.redox.2019.101266","article-title":"CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-\u03baB activation","volume":"26","author":"Lu","year":"2019","journal-title":"Redox Biol"},{"key":"B19-20250825","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1097\/01.ASN.0000130562.90255.8F","article-title":"Mouse model of X-linked Alport syndrome","volume":"15","author":"Rheault","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B20-20250825","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/ndt\/gfx246","article-title":"STAT3 inhibition attenuates the progressive phenotypes of Alport syndrome mouse model","volume":"33","author":"Yokota","year":"2018","journal-title":"Nephrol Dial Transplant"},{"key":"B21-20250825","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1080\/0886022X.2021.1896548","article-title":"The role of discoidin domain receptor 2 in the renal dysfunction of Alport syndrome mouse model","volume":"43","author":"Sannomiya","year":"2021","journal-title":"Ren Fail"},{"key":"B22-20250825","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1038\/s41598-021-86109-1","article-title":"Metformin ameliorates the severity of experimental Alport syndrome","volume":"11","author":"Omachi","year":"2021","journal-title":"Sci Rep"},{"key":"B23-20250825","doi-asserted-by":"crossref","first-page":"e0183959","DOI":"10.1371\/journal.pone.0183959","article-title":"Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome","volume":"12","author":"Yokota","year":"2017","journal-title":"PLoS One"},{"key":"B24-20250825","doi-asserted-by":"crossref","first-page":"e43852","DOI":"10.1371\/journal.pone.0043852","article-title":"Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome","volume":"7","author":"Koga","year":"2012","journal-title":"PLoS One"},{"key":"B25-20250825","doi-asserted-by":"crossref","first-page":"e71519","DOI":"10.1371\/journal.pone.0071519","article-title":"Reliability of transcutaneous measurement of renal function in various strains of conscious mice","volume":"8","author":"Schock-Kusch","year":"2013","journal-title":"PLoS One"},{"key":"B26-20250825","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 discovery","volume":"59","author":"Davies","year":"2016","journal-title":"J Med Chem"},{"key":"B27-20250825","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.kint.2019.04.027","article-title":"Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and Stage 4 chronic kidney disease","volume":"96","author":"Rossing","year":"2019","journal-title":"Kidney Int"},{"key":"B28-20250825","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-981-13-8871-2_10","article-title":"Role of podocyte injury in glomerulosclerosis","volume":"1165","author":"Lu","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B29-20250825","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1681\/ASN.2020050572","article-title":"Synaptopodin is dispensable for normal podocyte homeostasis but is protective in the context of acute podocyte injury","volume":"31","author":"Ning","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"B30-20250825","doi-asserted-by":"crossref","first-page":"F12","DOI":"10.1152\/ajprenal.00035.2021","article-title":"Synaptopodin deficiency exacerbates kidney disease in a mouse model of Alport Syndrome","volume":"321","author":"Ning","year":"2021","journal-title":"Am J Physiol Physiol"},{"key":"B31-20250825","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3390\/ijms21010263","article-title":"Inflammation and oxidative stress in chronic kidney disease\u2014Potential therapeutic role of minerals, vitamins and plant-derived metabolites","volume":"21","author":"Rapa","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B32-20250825","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s41100-018-0195-2","article-title":"Oxidative stress in chronic kidney disease","volume":"4","author":"Ling","year":"2018","journal-title":"Renal Replace Ther"},{"key":"B33-20250825","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1158\/1078-0432.CCR-08-2822","article-title":"Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer","volume":"15","author":"Homma","year":"2009","journal-title":"Clin Cancer Res"},{"key":"B34-20250825","doi-asserted-by":"crossref","first-page":"5821","DOI":"10.1038\/onc.2008.188","article-title":"Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling","volume":"27","author":"Reddy","year":"2008","journal-title":"Oncogene"},{"key":"B35-20250825","doi-asserted-by":"crossref","first-page":"e0207949","DOI":"10.1371\/journal.pone.0207949","article-title":"NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism","volume":"13","author":"M\u00e1rton","year":"2018","journal-title":"PLoS One"},{"key":"B36-20250825","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1038\/s41598-021-81021-0","article-title":"Nrf2 regulates cell motility through RhoA-ROCK1 signalling in non-small-cell lung cancer cells","volume":"11","author":"Ko","year":"2021","journal-title":"Sci Rep"},{"issue":"Pt B","key":"B37-20250825","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.freeradbiomed.2015.04.036","article-title":"The emerging role of Nrf2 in mitochondrial function","volume":"88","author":"Dinkova-Kostova","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"B38-20250825","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cotox.2016.10.002","article-title":"The multifaceted role of Nrf2 in mitochondrial function","volume":"1","author":"Holmstr\u00f6m","year":"2016","journal-title":"Curr Opin Toxicol"},{"key":"B39-20250825","doi-asserted-by":"crossref","first-page":"e000387","DOI":"10.1136\/lupus-2020-000387","article-title":"Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lpr mice [published correction appears in Lup Sci Med 7: E000387corr1, 2020 10.1136\/lupus-2020-000387corr1]","volume":"7","author":"Fortner","year":"2020","journal-title":"Lupus Sci Med"},{"key":"B40-20250825","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.redox.2016.12.022","article-title":"The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2\/PINK1","volume":"11","author":"Xiao","year":"2017","journal-title":"Redox Biol"},{"key":"B41-20250825","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1002\/art.38782","article-title":"Prevention of murine lupus nephritis by targeting multiple signaling axes and oxidative stress using a synthetic triterpenoid","volume":"66","author":"Wu","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B42-20250825","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbi.2015.11.018","article-title":"Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet","volume":"243","author":"Camer","year":"2016","journal-title":"Chem Biol Interact"},{"key":"B43-20250825","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3109\/00498254.2013.852705","article-title":"The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease","volume":"44","author":"Aminzadeh","year":"2014","journal-title":"Xenobiotica"},{"key":"B44-20250825","doi-asserted-by":"crossref","first-page":"F808","DOI":"10.1152\/ajprenal.00376.2012","article-title":"Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects","volume":"304","author":"Zoja","year":"2013","journal-title":"Am J Physiol Renal Physiol"},{"key":"B45-20250825","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/ki.2011.407","article-title":"Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy","volume":"81","author":"Gross","year":"2012","journal-title":"Kidney Int"},{"key":"B46-20250825","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ckj\/sfaa198","article-title":"SGLT2 inhibitors for non-diabetic kidney disease: Drugs to treat CKD that also improve glycaemia","volume":"13","author":"Fernandez-Fernandez","year":"2020","journal-title":"Clin Kidney J"},{"key":"B47-20250825","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.2337\/db20-1126","article-title":"Overexpression of Nrf2 in renal proximal tubular cells stimulates sodium-glucose cotransporter 2 expression and exacerbates dysglycemia and kidney injury in diabetic mice","volume":"70","author":"Zhao","year":"2021","journal-title":"Diabetes"},{"key":"B48-20250825","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1681\/ASN.2009060593","article-title":"Avosentan for overt diabetic nephropathy","volume":"21","author":"Mann","year":"2010","journal-title":"J Am Soc Nephrol"}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0004572021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:58:19Z","timestamp":1786478299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0004572021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0004572021","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"assertion":[{"value":"2021-07-12","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}