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Different treatment options have been developed for melanoma depending on the stage of the disease. Despite recent advances in immuno\u2010 and targeted therapies, advanced melanoma remains incurable and thus an urgent need persists for safe and more effective melanoma therapeutics. In this study, we demonstrate that a novel compound MM902 (3\u2010(3\u2010(bromomethyl)\u20105\u2010(4\u2010(<jats:italic>tert<\/jats:italic>\u2010butyl) phenyl)\u20101H\u20101,2,4\u2010triazol\u20101\u2010yl) phenol) exhibited potent efficacies in inhibiting the growth of different cancer cells, and suppressed tumor growth in a mouse xenograft model of malignant melanoma. Beginning with MM902 instead of specific targets, computational similarity\u2010 and docking\u2010based approaches were conducted to search for known anticancer drugs whose structural features match MM902 and whose pharmacological target would accommodate an irreversible inhibitor. Peroxisome proliferator\u2010activated receptor (PPAR) was computationally identified as one of the pharmacological targets and confirmed by in vitro biochemical assays. MM902 was shown to bind to PPAR\u03b3 in an irreversible mode of action and to function as a selective antagonist for PPAR\u03b3 over PPAR\u03b1 and PPAR\u03b4. It is hoped that MM902 will serve as a valuable research probe to study the functions of PPAR\u03b3 in tumorigenesis and other pathological processes.<\/jats:p>","DOI":"10.1002\/prp2.693","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T05:12:28Z","timestamp":1607231548000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of an irreversible PPAR\u03b3 antagonist with potent anticancer activity"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4797-995X","authenticated-orcid":false,"given":"Youyi","family":"Peng","sequence":"first","affiliation":[{"name":"Biomedical Informatics Shared Resource Cancer Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick NJ 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