{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:16:38Z","timestamp":1791504998899,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The natural product elaiophylin is a macrodiolide with a broad range of biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein\u2013protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here, we elaborated that elaiophylin likewise disrupts the Hsp90\/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similarly to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1\u03b1, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 and MIA-PaCa-2 3D spheroid formation. Finally, a strong inhibition of MDA-MB-231 cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90\/ Cdc37 interface as a target site.<\/jats:p>","DOI":"10.3390\/biom11060836","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T11:12:13Z","timestamp":1622805133000},"page":"836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Elaiophylin Is a Potent Hsp90\/ Cdc37 Protein Interface Inhibitor with K-Ras Nanocluster Selectivity"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-2363","authenticated-orcid":false,"given":"Farid A.","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-7251","authenticated-orcid":false,"given":"Vladimir","family":"Vukic","sequence":"additional","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, 20520 Turku, Finland"},{"name":"Faculty of Technology, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4135-8020","authenticated-orcid":false,"given":"Tiina A.","family":"Salminen","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, \u00c5bo Akademi University, 20520 Turku, Finland"},{"name":"InFLAMES Research Flagship Center, \u00c5bo Akademi University, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-0745","authenticated-orcid":false,"given":"Daniel","family":"Abankwa","sequence":"additional","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, 20520 Turku, Finland"},{"name":"Cancer Cell Biology and Drug Discovery Group, Department of Life Sciences and Medicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gui, M., Zhang, M.X., Wu, W.H., and Sun, P. 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