{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:30:38Z","timestamp":1774477838284,"version":"3.50.1"},"reference-count":233,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006742","name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio","doi-asserted-by":"publisher","award":["AntiMitoSphere_APSFCT_IINFACTS_2021"],"award-info":[{"award-number":["AntiMitoSphere_APSFCT_IINFACTS_2021"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio","doi-asserted-by":"publisher","award":["ActivCHIRAL_PI2RL_IINFACTS_2021"],"award-info":[{"award-number":["ActivCHIRAL_PI2RL_IINFACTS_2021"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA\u2019s effectiveness. With the desire to overcome some of the MTA\u2019s limitations, mitotic and SAC components have attracted great interest as promising microtubule-independent targets, leading to the so-called second-generation antimitotics (SGAs). The identification of inhibitors against most of these targets, and the promising outcomes achieved in preclinical assays, has sparked the interest of academia and industry. Many of these inhibitors have entered clinical trials; however, they exhibited limited efficacy as monotherapy, and failed to go beyond phase II trials. Combination therapies are emerging as promising strategies to give a second chance to these SGAs. Here, an updated view of the SGAs that reached clinical trials is here provided, together with future research directions, focusing on inhibitors that target the SAC components.<\/jats:p>","DOI":"10.3390\/pharmaceutics13071011","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T10:06:34Z","timestamp":1625220394000},"page":"1011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Second-Generation Antimitotics in Cancer Clinical Trials"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-9807","authenticated-orcid":false,"given":"Pedro","family":"Novais","sequence":"first","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"},{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, s\/n, 4169-007 Porto, Portugal"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-7321","authenticated-orcid":false,"given":"Patr\u00edcia M. A.","family":"Silva","sequence":"additional","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"}]},{"given":"Isabel","family":"Amorim","sequence":"additional","affiliation":[{"name":"GreenUPorto (Sustainable Agrifood Production) Research Center, Faculty of Sciences, University of Porto, Rua do Campo Alegre, s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-5779","authenticated-orcid":false,"given":"Hassan","family":"Bousbaa","sequence":"additional","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1242\/dev.091744","article-title":"Cdks, cyclins and CKIs: Roles beyond cell cycle regulation","volume":"140","author":"Lim","year":"2013","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ceb.2010.08.007","article-title":"Mechanisms of Aneuploidy","volume":"23","author":"Compton","year":"2011","journal-title":"Curr. 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