{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:19:43Z","timestamp":1783037983393,"version":"3.54.6"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Peptides"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.peptides.2026.171500","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:30:45Z","timestamp":1781566245000},"page":"171500","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Structure-based rational design of high-affinity JAZF1 variants peptides to target the testicular orphan nuclear receptor 4 and pro-opiomelanocortin axis in Cushing\u2019s disease"],"prefix":"10.1016","volume":"198","author":[{"given":"Wang","family":"Guoguo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.peptides.2026.171500_bib1","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1210\/me.2007-0181","article-title":"Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4","volume":"22","author":"Chen","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib2","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1128\/MCB.25.7.2722-2732.2005","article-title":"Deficits in motor coordination with aberrant cerebellar development in mice lacking testicular orphan nuclear receptor 4","volume":"25","author":"Chen","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.peptides.2026.171500_bib3","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.2337\/db10-0393","article-title":"Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity","volume":"60","author":"Kim","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.peptides.2026.171500_bib4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1477-7827-10-43","article-title":"Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis","volume":"10","author":"Lin","year":"2012","journal-title":"Reprod. Biol. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib5","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1210\/me.2010-0455","article-title":"Mice lacking TR4 nuclear receptor develop mitochondrial myopathy with deficiency in complex I","volume":"25","author":"Liu","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib6","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1073\/pnas.91.13.6040","article-title":"Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily","volume":"91","author":"Chang","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib7","first-page":"12215","article-title":"Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor","volume":"272","author":"Lee","year":"1997","journal-title":"A Modul. Thyroid. Horm. Target. Genes. J. Biol. Chem."},{"key":"10.1016\/j.peptides.2026.171500_bib8","doi-asserted-by":"crossref","first-page":"13437","DOI":"10.1074\/jbc.273.22.13437","article-title":"Negative feedback control of the retinoid-retinoic acid\/retinoid X receptor pathway by the human TR4 orphan receptor, a member of the steroid receptor superfamily","volume":"273","author":"Lee","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.peptides.2026.171500_bib9","doi-asserted-by":"crossref","first-page":"14724","DOI":"10.1073\/pnas.96.26.14724","article-title":"Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily","volume":"96","author":"Lee","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib10","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1210\/me.2013-1422","article-title":"Minireview: Pathophysiological roles of the TR4 nuclear receptor: lessons learned from mice lacking TR4","volume":"28","author":"Lin","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib11","doi-asserted-by":"crossref","first-page":"T99","DOI":"10.1530\/JME-15-0289","article-title":"60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression","volume":"56","author":"Drouin","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib12","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1152\/physrev.00024.2017","article-title":"POMC: The Physiological Power of Hormone Processing","volume":"98","author":"Harno","year":"2018","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.peptides.2026.171500_bib13","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1073\/pnas.75.2.669","article-title":"Characterization of pro-opiocortin, a precursor to opioid peptides and corticotropin","volume":"75","author":"Rubinstein","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib14","doi-asserted-by":"crossref","DOI":"10.1507\/endocrj.EJ24-0153","article-title":"Osilodrostat treatment in patients with Cushing's disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4)","author":"Shimatsu","year":"2024","journal-title":"Endocr. J."},{"key":"10.1016\/j.peptides.2026.171500_bib15","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15020496","article-title":"Advances in Molecular Pathophysiology and Targeted Therapy for Cushing's Disease","volume":"15","author":"Takayasu","year":"2023","journal-title":"Cancers"},{"key":"10.1016\/j.peptides.2026.171500_bib16","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s11102-012-0427-3","article-title":"Pituitary-directed medical therapy with pasireotide for a corticotroph macroadenoma: pituitary volume reduction and literature review","volume":"15","author":"Shimon","year":"2012","journal-title":"Pituitary"},{"key":"10.1016\/j.peptides.2026.171500_bib17","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2213628119","article-title":"Deletion of Jazf1 gene causes early growth retardation and insulin resistance in mice","volume":"119","author":"Lee","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib18","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1093\/nar\/gkac1259","article-title":"Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation","volume":"51","author":"Liu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.peptides.2026.171500_bib19","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1093\/nar\/gkh741","article-title":"TIP27: a novel repressor of the nuclear orphan receptor TAK1\/TR4","volume":"32","author":"Nakajima","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.peptides.2026.171500_bib20","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1182\/blood-2007-07-102061","article-title":"Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets","volume":"110","author":"Rix","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.peptides.2026.171500_bib21","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1074\/jbc.M110.168740","article-title":"The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor","volume":"286","author":"Zhou","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.peptides.2026.171500_bib22","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1111\/jcmm.16074","article-title":"Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells","volume":"25","author":"Xia","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.peptides.2026.171500_bib23","doi-asserted-by":"crossref","first-page":"30625","DOI":"10.1021\/acsomega.0c04623","article-title":"Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening","volume":"5","author":"Xia","year":"2020","journal-title":"ACS Omega"},{"key":"10.1016\/j.peptides.2026.171500_bib24","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1210\/jc.2016-1379","article-title":"Testicular Receptor-4: Novel Regulator of Glucocorticoid Resistance","volume":"101","author":"Zhang","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.peptides.2026.171500_bib25","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s11102-022-01254-8","article-title":"Pituitary surgery in Cushing's disease: first line treatment and role of reoperation","volume":"25","author":"Jones","year":"2022","journal-title":"Pituitary"},{"key":"10.1016\/j.peptides.2026.171500_bib26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1210\/en.2003-0669","article-title":"Hypothalamic-pituitary cytokine network","volume":"145","author":"Kariagina","year":"2004","journal-title":"Endocrinology"},{"key":"10.1016\/j.peptides.2026.171500_bib27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s12020-015-0601-2","article-title":"Clinical management of critically ill patients with Cushing\u2019s disease due to ACTH-secreting pituitary macroadenomas: effectiveness of presurgical treatment with pasireotide","volume":"52","author":"Cannavo","year":"2015","journal-title":"Endocrine"},{"key":"10.1016\/j.peptides.2026.171500_bib28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.mce.2018.07.007","article-title":"Metformin suppresses growth and adrenocorticotrophic hormone secretion in mouse pituitary corticotroph tumor AtT20\u00a0cells","volume":"478","author":"Jin","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib29","first-page":"425","article-title":"Clinical use of pasireotide for Cushing's disease in adults","volume":"11","author":"Ceccato","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"10.1016\/j.peptides.2026.171500_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2021.101490","article-title":"Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide","volume":"35","author":"Varlamov","year":"2021","journal-title":"Best. Pract. & Res. Clin. Endocrinol. & Metab."},{"key":"10.1016\/j.peptides.2026.171500_bib31","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1530\/EJE-09-0098","article-title":"Merits and pitfalls of mifepristone in Cushing's syndrome","volume":"160","author":"Castinetti","year":"2009","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.peptides.2026.171500_bib32","doi-asserted-by":"crossref","first-page":"13353","DOI":"10.1073\/pnas.0905724106","article-title":"TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation","volume":"106","author":"Xie","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/bs.ctdb.2017.02.002","article-title":"TR2 and TR4 Orphan Nuclear Receptors: An Overview","volume":"125","author":"Lin","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.peptides.2026.171500_bib34","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1074\/mcp.M600180-MCP200","article-title":"Modulation of testicular receptor 4 activity by mitogen-activated protein kinase-mediated phosphorylation","volume":"5","author":"Huq","year":"2006","journal-title":"Mol. Cell. Proteom."},{"key":"10.1016\/j.peptides.2026.171500_bib35","doi-asserted-by":"crossref","first-page":"21129","DOI":"10.1074\/jbc.M110.208181","article-title":"Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation","volume":"286","author":"Xie","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.peptides.2026.171500_bib36","doi-asserted-by":"crossref","first-page":"7709","DOI":"10.1074\/jbc.M207116200","article-title":"Identification of a novel testicular orphan receptor-4 (TR4)-associated protein as repressor for the selective suppression of TR4-mediated transactivation","volume":"278","author":"Yang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.peptides.2026.171500_bib37","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1073\/pnas.1306182110","article-title":"Evidence for orphan nuclear receptor TR4 in the etiology of Cushing disease","volume":"110","author":"Du","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.peptides.2026.171500_bib38","first-page":"373","article-title":"Rat and mouse proopiomelanocortin gene sequences target tissue-specific expression to the pituitary gland but not to the hypothalamus of transgenic mice","volume":"58","author":"Rubinstein","year":"1993","journal-title":"Neuroendocrinology"},{"key":"10.1016\/j.peptides.2026.171500_bib39","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1128\/MCB.25.8.3076-3086.2005","article-title":"Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting","volume":"25","author":"de Souza","year":"2005","journal-title":"Mol. Cell. Biol."}],"container-title":["Peptides"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0196978126000379?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0196978126000379?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:57:56Z","timestamp":1783036676000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0196978126000379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":39,"alternative-id":["S0196978126000379"],"URL":"https:\/\/doi.org\/10.1016\/j.peptides.2026.171500","relation":{},"ISSN":["0196-9781"],"issn-type":[{"value":"0196-9781","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-based rational design of high-affinity JAZF1 variants peptides to target the testicular orphan nuclear receptor 4 and pro-opiomelanocortin axis in Cushing\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"Peptides","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.peptides.2026.171500","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"171500"}}