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The emergence of drug resistance and limited arsenal of antifungal agents further aggravates\u2009the current\u2009situation resulting in a growing challenge in medical mycology. Here, we identified that ponatinib, an FDA\u2010approved antitumour drug, significantly enhanced the activity of the azole fluconazole, the most widely used antifungal drug. Further detailed investigation of ponatinib revealed that its combination with fluconazole displayed broad\u2010spectrum synergistic interactions against a variety of human fungal pathogens such as\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    ,\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    and\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    . Mechanistic insights into the mode of action unravelled that ponatinib reduced the efflux of fluconazole via Pdr5 and suppressed the expression of the proton pump, Pma1. Taken together, our study identifies ponatinib as a novel antifungal that enhances drug activity of fluconazole against diverse fungal pathogens.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.13814","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T22:00:02Z","timestamp":1620338402000},"page":"482-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Repurposing the FDA\u2010approved anticancer agent ponatinib as a fluconazole potentiator by suppression of multidrug efflux and Pma1 expression in a broad spectrum of yeast species"],"prefix":"10.1111","volume":"15","author":[{"given":"Lin","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes Center for Single\u2010Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine Shanghai 200025 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