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In our study, we found PKM2 is highly expressed in melanoma patients and the malignance is positively correlated with high PKM2 activity and glycolytic capability in melanoma cells. Suppression of PKM2 expression by knocking down markedly attenuated malignant phenotype both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and restoration of PKM2 expression in PKM2 depleted cells could rescue melanoma cells proliferation, invasion and metastasis. With the data indicating PKM2 as a potential therapeutic target, we performed screening for PKM2 inhibitors and identified benserazide (Ben), a drug currently in clinical use. We demonstrated that Ben directly binds to and blocks PKM2 enzyme activity, leading to inhibition of aerobic glycolysis concurrent up\u2010regulation of OXPHOS. Of note, despite PKM2 is very similar to PKM1, Ben does not affect PKM1 enzyme activity. We showed that Ben significantly inhibits cell proliferation, colony formation, invasion and migration\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The specificity of Ben was demonstrated by the findings that, suppression of PKM2 expression diminishes the efficacy of Ben in inhibition of melanoma cell growth; ectopic PKM2 expression in normal cells sensitizes cells to Ben treatment. Interestingly, PKM2 activity and aerobic glycolysis are upregulated in BRAFi\u2010resistant melanoma cells. As a result, BRAFi\u2010resistant cells exhibit heightened sensitivity to suppression of PKM2 expression or treatment with Ben both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/ijc.32756","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T12:37:41Z","timestamp":1572007061000},"page":"139-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Benserazide is a novel inhibitor targeting PKM2 for melanoma treatment"],"prefix":"10.1002","volume":"147","author":[{"given":"Youyou","family":"Zhou","sequence":"first","affiliation":[{"name":"The Department of Dermatology, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital Central South 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