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Due to its oncogenic activities and overexpression in a majority of human cancers, it is an interesting target for novel drug therapies. <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> binding to the E\u2010box (5\u2032\u2010<jats:styled-content style=\"fixed-case\">CACGTGT<\/jats:styled-content>\u20103\u2032) sequence at gene promoters contributes to more than 4000 <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>\u2010dependent transcripts. Owing to its importance in <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> regulation, we designed a novel sequence\u2010specific <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding pyrrole\u2013imidazole (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>) polyamide, Myc\u20105, that recognizes the E\u2010box consensus sequence. Bioinformatics analysis revealed that the Myc\u20105 binding sequence appeared in 5\u2032\u2010 <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> binding E\u2010box sequences at the <jats:styled-content style=\"fixed-case\">eIF<\/jats:styled-content>4G1, <jats:styled-content style=\"fixed-case\">CCND<\/jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>4 gene promoters. Furthermore, Ch<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content> coupled with detection by quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> indicated that Myc\u20105 has the ability to inhibit <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> binding at the target gene promoters and thus cause downregulation at the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level and protein expression of its target genes in human Burkitt's lymphoma model cell line, P493.6, carrying an inducible <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> repression system and the K562 (human chronic myelogenous leukemia) cell line. Single i.v. injection of Myc\u20105 at 7.5\u00a0mg\/kg dose caused significant tumor growth inhibition in a <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>\u2010dependent tumor xenograft model without evidence of toxicity. We report here a compelling rationale for the identification of a <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content> polyamide that inhibits a part of E\u2010box\u2010mediated <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> downstream gene expression and is a model for showing that phenotype\u2010associated <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content> downstream gene targets consequently inhibit <jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>\u2010dependent tumor growth.<\/jats:p>","DOI":"10.1111\/cas.12610","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T10:57:40Z","timestamp":1421924260000},"page":"421-429","source":"Crossref","is-referenced-by-count":16,"title":["Identification of a novel E\u2010box binding pyrrole\u2010imidazole polyamide inhibiting <scp>MYC<\/scp>\u2010driven cell 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