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Here, we reviewed the proposed mechanisms of the physiological activity of the quinazoline derivative EVP4593 and perspectives for its clinical implication. We summarized the accumulated data about EVP4593 and focused on its activities in different models of Huntington\u2019s disease (HD), including patient-specific iPSCs-based neurons. To make a deeper insight into its neuroprotective role in HD treatment, we discussed the ability of EVP4593 to modulate calcium signaling and reduce the level of the huntingtin protein. Moreover, we described possible protective effects of EVP4593 in other pathologies, such as oncology, cardiovascular diseases and parasite invasion. We hope that comprehensive analyses of the molecular mechanisms of EVP4593 activity will allow for the expansion of the scope of the EVP4593 application.<\/jats:p>","DOI":"10.3390\/ijms232415724","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T01:42:27Z","timestamp":1670809347000},"page":"15724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington\u2019s Disease and Other Human Pathologies"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2338-6252","authenticated-orcid":false,"given":"Dmitriy A.","family":"Grekhnev","sequence":"first","affiliation":[{"name":"Laboratory of Ionic Channels of Cell Membranes, Department of Molecular Physiology of the Cell, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Kruchinina","sequence":"additional","affiliation":[{"name":"Laboratory of Ionic Channels of Cell Membranes, Department of Molecular Physiology of the Cell, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-7316","authenticated-orcid":false,"given":"Vladimir A.","family":"Vigont","sequence":"additional","affiliation":[{"name":"Laboratory of Ionic Channels of Cell Membranes, Department of Molecular Physiology of the Cell, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-1188","authenticated-orcid":false,"given":"Elena V.","family":"Kaznacheyeva","sequence":"additional","affiliation":[{"name":"Laboratory of Ionic Channels of Cell Membranes, Department of Molecular Physiology of the Cell, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,11]]},"reference":[{"key":"ref_1","first-page":"395637","article-title":"Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives","volume":"2014","author":"Asif","year":"2014","journal-title":"Int. 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