{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:28:29Z","timestamp":1760315309837,"version":"build-2065373602"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2025,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human antigen R (HuR) is an RNA binding protein (RBP) belonging to the ELAV (Embryonic Lethal Abnormal Vision) family, which stabilizes mRNAs and regulates the expression of multiple genes. Its altered expression or localization is related to pathological features such as cancer or inflammation. Dihydrotanshinone I (DHTS I) is a naturally occurring, tetracyclic ortho\u2010quinone inhibitor of the HuR\u2010mRNA interaction. Our earlier efforts led to the identification of a synthetic Tanshinone Mimic (TM) <jats:bold>2<\/jats:bold> with improved affinity for HuR. Here we report five new TM probes <jats:bold>3\u20135<\/jats:bold> bearing a detection\u2010promoting moiety (either photo affinity probe \u2010 PAP or biotin) as a para\u2010substituent on the phenyl\u2010sulphonamide for mechanism of action (MoA) studies. Biological and biochemical assays were used to characterize the novel TM conjugates <jats:bold>3\u20135<\/jats:bold>. They showed similar toxic activity in HuR\u2010expressing triple\u2010negative breast cancer MDA\u2010MB\u2010231 cells, with micromolar CC<jats:sub>50<\/jats:sub>s. REMSAs revealed that photoactivatable groups (<jats:bold>4\u2009a<\/jats:bold> and <jats:bold>4\u2009b<\/jats:bold>), but not biotin (<jats:bold>5\u2009a<\/jats:bold> and <jats:bold>5\u2009b<\/jats:bold>), prevented conjugates\u2019 ability to disrupt rHuR\u2010RNA complexes. Further biochemical studies confirmed that biotinylated probes, in particular <jats:bold>5\u2009a<\/jats:bold>, can be used to isolate rM1\u2005M2 from solutions, taking advantage of streptavidin\u2010coated magnetic beads, thus being the most promising HuR inhibitor to be used for further MoA studies in cell lysates.<\/jats:p>","DOI":"10.1002\/cbic.202400917","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:04:28Z","timestamp":1734325468000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Preliminary Evaluation of Tanshinone Mimic Conjugates for Mechanism of Action Studies"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0698-8320","authenticated-orcid":false,"given":"Giulia","family":"Assoni","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milan Italy"},{"name":"Department CIBIO University of Trento  Via Sommarive 9 38122 Trento Italy"},{"name":"Present address: Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences ETH Zurich  Vladimir-Prelog-Weg 1-5\/10, ETH Hoenggerberg, HCI H494 8093 Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1gata Sofia Assun\u00e7\u00e3o","family":"Carreira","sequence":"additional","affiliation":[{"name":"Department CIBIO University of Trento  Via Sommarive 9 38122 Trento Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Tomiello","sequence":"additional","affiliation":[{"name":"Department CIBIO University of Trento  Via Sommarive 9 38122 Trento Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-7344","authenticated-orcid":false,"given":"Pierfausto","family":"Seneci","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1652-3415","authenticated-orcid":false,"given":"Alessandro","family":"Provenzani","sequence":"additional","affiliation":[{"name":"Department CIBIO University of Trento  Via Sommarive 9 38122 Trento Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-3504","authenticated-orcid":false,"given":"Daniela","family":"Arosio","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche (SCITEC) 'Giulio Natta' Consiglio Nazionale delle Ricerche (CNR)  Via C. 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