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To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.<\/jats:p>","DOI":"10.1073\/pnas.1210371110","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T21:28:16Z","timestamp":1355261296000},"page":"21360-21365","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":500,"title":["Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation"],"prefix":"10.1073","volume":"109","author":[{"given":"Wei","family":"Qi","sequence":"first","affiliation":[{"name":"China Novartis Institutes for BioMedical Research, Shanghai 201203, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HoMan","family":"Chan","sequence":"additional","affiliation":[{"name":"China Novartis Institutes for BioMedical Research, Shanghai 201203, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Teng","sequence":"additional","affiliation":[{"name":"China Novartis Institutes for BioMedical Research, Shanghai 201203, China; 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