{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:52:06Z","timestamp":1791888726825,"version":"4.3.4"},"reference-count":83,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H03823"],"award-info":[{"award-number":["23H03823"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K01635"],"award-info":[{"award-number":["24K01635"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27111"],"award-info":[{"award-number":["23K27111"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mycalolides are marine\u2010derived trisoxazole macrolides that exhibit potent actin\u2010depolymerizing activity and inhibit the proliferation, migration, and invasion of various cancer cells. The C25\u2013C35 side\u2010chain moiety of mycalolides is important for their actin\u2010binding properties; however, the biological function of the C1\u2013C24 trisoxazole macrolactone moiety remains largely unexplored. In this study, using a photoaffinity biotin probe, we identified tubulin as a new, actin\u2010independent target of mycalolide C (MyC). Ultracentrifugation, fluorescence\u2010based tubulin polymerization assays, and transmission electron microscopy of negatively stained microtubules (MTs) demonstrated that MyC and trisoxazole macrolactones exert potent synergistic effects on paclitaxel\u2010induced MT assembly and stabilization. These compounds enhanced the antiproliferative activity of paclitaxel by 4.2\u2010 to 6.7\u2010fold in HCT\u2010116 human colon cancer cells but showed little synergy in 3T3\u2010L1 murine fibroblast. Molecular modeling studies suggest that MyC stabilizes the protein\u2013protein interactions between \u03b1\/\u03b2\u2010tubulin heterodimers. Given that the C1\u2013C24 trisoxazole macrolactone moiety and its analogues exhibit little cytotoxicity, our findings may contribute to the development of new lead compounds for MT inhibitors with reduced side effects.<\/jats:p>","DOI":"10.1002\/anie.202522954","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T12:09:50Z","timestamp":1773749390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Trisoxazole Macrolides Potentiate the Microtubule Assembly and Antimitotic Activities of Taxanes"],"prefix":"10.1002","volume":"65","author":[{"given":"Shohei","family":"Ebihara","sequence":"first","affiliation":[{"name":"Graduate School of Bioagricultural Sciences Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rio","family":"Takaiso","sequence":"additional","affiliation":[{"name":"Graduate School of Bioagricultural Sciences Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunori","family":"Oshima","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"},{"name":"Cellular and Structural Physiology Institute (CeSPI) Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"},{"name":"Institute For Glyco\u2010core Research (iGCORE) Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"},{"name":"Center For One Medicine Innovative Translational Research (COMIT) Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"},{"name":"Institute of Quantum Chemistry Innovation Institutes of Innovation for Future Society Nagoya University Furo\u2010Cho Chikusa Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6685-4461","authenticated-orcid":false,"given":"Masaki","family":"Kita","sequence":"additional","affiliation":[{"name":"Graduate School of Bioagricultural Sciences Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"},{"name":"Promotion Office for Open Innovation, Institutes of Innovation for Future Society Nagoya University Furo\u2010Cho Chikusa  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00759"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","unstructured":"J. E.Ishmael J. D.Serrill X.Wan A. W.Alani andK. L.McPhail \u201cMacrocyclic Marine Natural Products: Leads in the Drug Discovery Process for Potential Glioma Therapeutics \u201dFaseb Journal30(2016): 1272.10 https:\/\/doi.org\/10.1096\/fasebj.30.1_supplement.1272.10.","DOI":"10.1096\/fasebj.30.1_supplement.1272.10"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(00)99131\u20107"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja990817w"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/np010663"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/md302029"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/np980102r"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201044036\u20102"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20105793(93)81557\u2010G"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)43938\u20105"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a022029"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50121a025"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00264a052"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00267a024"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00256a021"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.04.069"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50095a021"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00264a053"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2233339100"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201200385"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.12.052"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2012.11.001"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201035284\u20109"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2004.05.078"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.06.046"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.02.068"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol300182r"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01532"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc050324i"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja310495p"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1006"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol036458y"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c12404"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja994003r"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja002377a"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(98)01257\u2010X"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/b000750l"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/b000751j"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200700459"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/b801036f"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200290057"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201507795"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2012.08.012"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00076a082"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00095a071"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/B800263K"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.86.176"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502089102"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2005.02.011"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201103802"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja406580w"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC04259A"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.20220299"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CC01304B"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0703\u2010599"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4NP00129J"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-99-1714-3_4"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201064321\u20109"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/asia.202200631"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/chemle\/upae142"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.09.044"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.04.049"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17853"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.9b01099"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)89437\u20106"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2018.08.058"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2010.07.046"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.59.2.267"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.01.001"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo991296y"},{"key":"e_1_2_7_72_1","first-page":"3356","article-title":"Peloruside A, a Novel Antimitotic Agent With Paclitaxel\u2010Like Microtubule\u2010stabilizing Activity","volume":"62","author":"Hood K. A.","year":"2002","journal-title":"Cancer Research"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.03.026"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201307749"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00146C"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9552"},{"key":"e_1_2_7_77_1","first-page":"816","article-title":"Mitotic Block Induced in HeLa Cells by Low Concentrations of Paclitaxel (Taxol) Results in Abnormal Mitotic Exit and Apoptotic Cell Death","volume":"56","author":"Jordan M. A.","year":"1996","journal-title":"Cancer Research"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601496"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp060101p"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027847"},{"key":"e_1_2_7_82_1","first-page":"96","volume":"1785","author":"McGrogan B. T.","year":"2008","journal-title":"BBA Reviews on Cancer"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100742"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2021.100754"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202522954","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202522954","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202522954","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:33:04Z","timestamp":1791887584000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202522954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":83,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,4,27]]}},"alternative-id":["10.1002\/anie.202522954"],"URL":"https:\/\/doi.org\/10.1002\/anie.202522954","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"assertion":[{"value":"2025-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22954"}}