{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:27:22Z","timestamp":1753878442823,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The MDM2\u2010p53 pathway plays a pivotal role in regulating cell cycle and apoptosis, with its dysfunction contributing to approximately 50% of human malignancies. MDM2, an E3 ubiquitin ligase, targets the tumour suppressor p53 for degradation, thereby promoting uncontrolled cell growth in cancers. Inhibiting the MDM2\u2010p53 interaction represents a promising therapeutic strategy for reactivating p53\u2019s tumour\u2010suppressive functions. This study explored the potential of ibutamoren (IBU) as a novel inhibitor of MDM2. In silico analyses utilizing molecular modelling revealed that IBU has a low IC<jats:sub>50<\/jats:sub> for MDM2 inhibition and favourably binds to the p53\u2010binding pocket of MDM2. In vitro experiments demonstrated that IBU treatment reduced the viability of immortalized cancer cell lines with a functional MDM2\u2010p53 pathway but not in cell lines where this pathway harboured damaging mutations. This trend was further supported by RT\u2010qPCR analysis, which showed differential expression of two p53 target genes upon IBU treatment in cell lines with wild MDM2\u2010p53 pathways but not in those harbouring damaging mutations. These findings provide preliminary evidence supporting IBU's anticancer activity, plausibly through the MDM2\u2010p53 pathway, and suggest that further studies are warranted to explore its mechanism of action and potential development as a lead compound in oncology research.<\/jats:p>","DOI":"10.1111\/bcpt.14111","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T04:04:50Z","timestamp":1734062690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the P53\u2010dependent anti\u2010cancer effect of ibutamoren in human cancer cell lines"],"prefix":"10.1111","volume":"136","author":[{"given":"Naeem","family":"Abdul Ghafoor","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Graduate School of Natural and Applied Sciences Mugla Sitki Kocman University  Mugla Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Rasuli","sequence":"additional","affiliation":[{"name":"UFR Biosciences Claude Bernard University Lyon 1  Villeurbanne France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zg\u00fcr","family":"Tanriverdi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine Mugla Sitki Kocman University  Mugla Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-7459","authenticated-orcid":false,"given":"Ay\u015feg\u00fcl","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Graduate School of Natural and Applied Sciences Mugla Sitki Kocman University  Mugla Turkey"},{"name":"Department of Molecular Biology and Genetics, Faculty of Science Mugla Sitki Kocman University  Mugla Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/20503121211034366"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants10102193"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.09.067"},{"key":"e_1_2_11_5_1","unstructured":"National Cancer Institute.Targeted therapy for cancer.2022.https:\/\/www.cancer.gov\/about-cancer\/treatment\/types\/targeted-therapies"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa666"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2014.10.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001347\u20101"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.27.20130030"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.68"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2023.101790"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201031484\u20100"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sxmr.2017.02.004"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5b00559"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c03471"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac956"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_11_20_1","unstructured":"DeLanoWL.2024.http:\/\/www.pymol.org\/pymol"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263\u20107855(96)00018\u20105"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4067"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0014475"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21787"},{"volume-title":"Maestro","year":"2024","author":"Schr\u00f6dinger LCC","key":"e_1_2_11_26_1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13944"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.010"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.9b03372"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109163"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149014"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010022\u201001314\u20103"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.502"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.14111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T02:19:20Z","timestamp":1737339560000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.14111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,12]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/bcpt.14111"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.14111","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"type":"print","value":"1742-7835"},{"type":"electronic","value":"1742-7843"}],"subject":[],"published":{"date-parts":[[2024,12,12]]},"assertion":[{"value":"2024-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14111"}}