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To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1\u2009\u03bcM GO-Y030, in a manner equivalent to 10\u2009\u00b5M curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice.<\/jats:p>","DOI":"10.1038\/s41598-020-64207-w","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T06:04:21Z","timestamp":1588053861000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Kana","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Sunagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Funamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Genpei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Katanasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurmila","family":"Sari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-939X","authenticated-orcid":false,"given":"Yoshiharu","family":"Iwabuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7331","authenticated-orcid":false,"given":"Hideaki","family":"Kakeya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-224X","authenticated-orcid":false,"given":"Hiromichi","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"64207_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1161\/CIRCRESAHA.113.300268","volume":"113","author":"VL Roger","year":"2013","unstructured":"Roger, V. 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