{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:36:12Z","timestamp":1753878972346,"version":"3.41.2"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019573","name":"Amsterdam University Medical Centers","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019573","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>CCAAT\/enhancer\u2010binding protein delta (C\/EBP\u03b4) has been shown to promote tumour growth, drug resistance and metastasis formation in some cancers, whereas we have shown that its re\u2010expression limits the features of tumour progression in pancreatic ductal adenocarcinoma (PDAC). The pharmacological targeting\u2014either activation or inhibition\u2014of C\/EBP\u03b4 may therefore harbour clinical relevance and is desirable for preclinical studies on C\/EBP\u03b4 in different contexts. Regrettably, to date, only few molecules have been identified that modify C\/EBP\u03b4. Here, we present a high\u2010throughput compound screen in conjunction with a novel eGFP reporter to identify further compounds that either increase or decrease C\/EBP\u03b4 transcriptional activity. Of 1402 small molecule inhibitors, we identified a total of 22 potent inducers and 18 inhibitors of C\/EBP\u03b4\u2010mediated eGFP fluorescence. Using pathway enrichment analysis, we found that, generally, inhibition of the cell cycle elicits an increase in C\/EBP\u03b4 activity whereas PI3K\/Akt\/mTOR\u2010targeting compounds reduce C\/EBP\u03b4 activity. We confirmed the potential importance of cell cycle\u2010mediated regulation of C\/EBP\u03b4 by showing that four of the most potent C\/EBP\u03b4 activators\u2014R547, PHA793387, AZD5438 and AT7519, all multi\u2010cyclin\u2010dependent kinase (CDK) inhibitors\u2014limited the clonal expansion of PDAC cells. Next to providing a valuable selection of C\/EBP\u03b4\u2010modulating compounds for the use in preclinical studies, this report contributes to our understanding of the molecular regulatory mechanisms of C\/EBP\u03b4 in general and in PDAC in particular.<\/jats:p>","DOI":"10.1111\/jcmm.70287","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T11:11:56Z","timestamp":1738321916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of C\/EBP\u03b4\u2010Modifying Compounds as Potential Anticancer Agents Using a High\u2010Throughput Drug Screen"],"prefix":"10.1111","volume":"29","author":[{"given":"Leonie","family":"Hartl","sequence":"first","affiliation":[{"name":"Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JanWillem","family":"Duitman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Experimental Immunology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Inflammatory Diseases Amsterdam Infection &amp; Immunity  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hella L.","family":"Aberson","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Paul","family":"Medema","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten F.","family":"Bijlsma","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-4068","authenticated-orcid":false,"given":"C. 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