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We have tested the effects of new pharmacological inhibitors of MRTF\/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF\/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF\/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC<jats:sub>50<\/jats:sub> of 5\u2009\u03bcM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0005) and 33% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF\/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues.<\/jats:p>","DOI":"10.1038\/s41598-017-00212-w","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T14:24:04Z","timestamp":1490624644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Local delivery of novel MRTF\/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Cynthia","family":"Yu-Wai-Man","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Spencer-Dene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M. 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