{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:04:35Z","timestamp":1753884275745,"version":"3.41.2"},"reference-count":24,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"name":"Erasmus+"},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004099","name":"La Ligue Contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-16-CE11-0017-01"],"award-info":[{"award-number":["ANR-16-CE11-0017-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione di Vignola"},{"name":"La Ligue R\u00e9gionale Contre le Cancer"},{"name":"La foundation pour la Recherche M\u00e9dicale","award":["DEQ20170336742"],"award-info":[{"award-number":["DEQ20170336742"]}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale; Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro. The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.<\/jats:p>","DOI":"10.1242\/jcs.239244","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T19:14:25Z","timestamp":1582571665000},"source":"Crossref","is-referenced-by-count":4,"title":["A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression"],"prefix":"10.1242","volume":"133","author":[{"given":"Vittoria","family":"Pirani","sequence":"first","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"},{"name":"University of Modena and Reggio Emilia 2 Department of Life Sciences , , 41125 Modena , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"M\u00e9tivier","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Gallaud","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Thomas","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siou","family":"Ku","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Chretien","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Ettari","sequence":"additional","affiliation":[{"name":"University of Messina 3 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences , , 98168 Messina , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9027-5849","authenticated-orcid":false,"given":"Regis","family":"Giet","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-2624","authenticated-orcid":false,"given":"Lorenzo","family":"Corsi","sequence":"additional","affiliation":[{"name":"University of Modena and Reggio Emilia 2 Department of Life Sciences , , 41125 Modena , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-2331","authenticated-orcid":false,"given":"Christelle","family":"Benaud","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes) - UMR 6290 1 , 35000 Rennes , France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"2024061319230897800_JCS239244C23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.critrevonc.2011.04.012","article-title":"Chemotherapy-induced peripheral neurotoxicity (CIPN): an update","volume":"82","author":"Argyriou","year":"2012","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"2024061319230897800_JCS239244C1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1083\/jcb.200307098","article-title":"AHNAK interaction with the annexin 2\/S100A10 complex regulates cell membrane cytoarchitecture","volume":"164","author":"Benaud","year":"2004","journal-title":"J. Cell Biol."},{"key":"2024061319230897800_JCS239244C2","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cub.2006.04.043","article-title":"Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint","volume":"16","author":"Brito","year":"2006","journal-title":"Curr. Biol."},{"key":"2024061319230897800_JCS239244C3","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1089\/104454999315178","article-title":"A His2AvDGFP fusion gene complements a lethal His2AvD mutant allele and provides an in vivo marker for Drosophila chromosome behavior","volume":"18","author":"Clarkson","year":"1999","journal-title":"DNA Cell Biol."},{"key":"2024061319230897800_JCS239244C4","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1083\/jcb.146.5.1005","article-title":"mini spindles: a gene encoding a conserved microtubule-associated protein required for the integrity of the mitotic spindle in Drosophila","volume":"146","author":"Cullen","year":"1999","journal-title":"J. Cell Biol."},{"key":"2024061319230897800_JCS239244C5","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1146\/annurev.cellbio.13.1.83","article-title":"Microtubule polymerization dynamics","volume":"13","author":"Desai","year":"1997","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2024061319230897800_JCS239244C6","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nrd3253","article-title":"Microtubule-binding agents: a dynamic field of cancer therapeutics","volume":"9","author":"Dumontet","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"2024061319230897800_JCS239244C7","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1083\/jcb.201311094","article-title":"Ensconsin\/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells","volume":"204","author":"Gallaud","year":"2014","journal-title":"J. Cell Biol."},{"key":"2024061319230897800_JCS239244C8","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.1242\/dev.029009","article-title":"PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte","volume":"135","author":"Gervais","year":"2008","journal-title":"Development"},{"key":"2024061319230897800_JCS239244C9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nrc3461","article-title":"Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics","volume":"13","author":"Gonzalez","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"2024061319230897800_JCS239244C10","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1038\/onc.2011.30","article-title":"Mitosis as an anti-cancer target","volume":"30","author":"Janssen","year":"2011","journal-title":"Oncogene"},{"key":"2024061319230897800_JCS239244C24","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nrc2803","article-title":"Microtubules and resistanace to tubulin-binding agents","volume":"10","author":"Kavallaris","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"2024061319230897800_JCS239244C11","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/jbiol195","article-title":"The nature of cell-cycle checkpoints: facts and fallacies","volume":"8","author":"Khodjakov","year":"2009","journal-title":"J. Biol."},{"key":"2024061319230897800_JCS239244C12","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1534\/g3.113.005777","article-title":"The genomic and transcriptomic landscape of a HeLa cell line","volume":"3","author":"Landry","year":"2013","journal-title":"G3"},{"key":"2024061319230897800_JCS239244C13","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/nmeth.1493","article-title":"Analysis of microtubule dynamic instability using a plus-end growth marker","volume":"7","author":"Matov","year":"2010","journal-title":"Nat. Methods"},{"key":"2024061319230897800_JCS239244C14","doi-asserted-by":"publisher","first-page":"2200","DOI":"10.1016\/j.bmc.2007.11.080","article-title":"Structure-activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-o ne as neuroprotective agent","volume":"16","author":"Micale","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"2024061319230897800_JCS239244C15","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/312237a0","article-title":"Dynamic instability of microtubule growth","volume":"312","author":"Mitchison","year":"1984","journal-title":"Nature"},{"key":"2024061319230897800_JCS239244C16","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.lfs.2016.03.051","article-title":"A novel 2,3-benzodiazepine-4-one derivative AMPA antagonist inhibits G2\/M transition and induces apoptosis in human leukemia Jurkat T cell line","volume":"152","author":"Parenti","year":"2016","journal-title":"Life Sci."},{"key":"2024061319230897800_JCS239244C17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nrm.2016.162","article-title":"Mitotic spindle assembly in animal cells: a fine balancing act","volume":"18","author":"Prosser","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2024061319230897800_JCS239244C18","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/med.20242","article-title":"Drugs that target dynamic microtubules: a new molecular perspective","volume":"31","author":"Stanton","year":"2011","journal-title":"Med. Res. Rev."},{"key":"2024061319230897800_JCS239244C19","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1007\/s00702-014-1182-6","article-title":"Glutamate and its receptors in cancer","volume":"121","author":"Stepulak","year":"2014","journal-title":"J. Neural Transm."},{"key":"2024061319230897800_JCS239244C20","doi-asserted-by":"publisher","first-page":"35149","DOI":"10.1074\/jbc.M113.522375","article-title":"Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex","volume":"288","author":"Tipton","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2024061319230897800_JCS239244C21","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.4161\/cc.5.22.3463","article-title":"Cell cycle synchronization at the G2\/M phase border by reversible inhibition of CDK1","volume":"5","author":"Vassilev","year":"2006","journal-title":"Cell Cycle"},{"key":"2024061319230897800_JCS239244C22","doi-asserted-by":"publisher","first-page":"E28","DOI":"10.1038\/35050669","article-title":"The spindle: a dynamic assembly of microtubules and motors","volume":"3","author":"Wittmann","year":"2001","journal-title":"Nat. Cell Biol."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/jcs.239244","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.239244\/3514178\/jcs239244.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.239244\/2062416\/jcs_239244v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.239244\/3514178\/jcs239244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T22:17:31Z","timestamp":1718317051000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/133\/7\/jcs239244\/224866\/A-novel-benzodiazepine-derivative-that-suppresses"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.239244","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"type":"electronic","value":"1477-9137"},{"type":"print","value":"0021-9533"}],"subject":[],"published":{"date-parts":[[2020,4,1]]},"article-number":"jcs239244"}}