In vitro activity: BRD7552 upregulates PDX1 expression in both primary human islets and ductal cells, and induces epigenetic changes in the PDX1 promoter consistent with transcriptional activation. BRD7552 increases PDX1 mRNA levels by 2- to 4-fold, with a maximal effect at 5 μM and the expression of MAFA. BRD7552 increases PDX1 expression in mouse αTC cells but not βTC cells. Treatment of PANC-1 cells with BRD7552 causes a dose-dependent increase in insulin mRNA expression.

Cell Assay: In human cells, BRD7552 upregulated the expression of PDX1 via epigenetically altering PDX1 promoter area. BRD7552 was discovered as a PDX1 inducer in a cell-based phenotypic screening assay. It was used to induce the expression of PDX1. In PANC-1 cells, BRD7552 up-regulated mRNA and protein levels of PDX1. BRD7552 changed epigenetic markers within the PDX1 promoter region that was consistent with transcriptional activation. In cell culture, BRD7552 partially complemented PDX1, enhancing insulin expression induced by the introduction of three genes in PANC-1 cells. In PANC-1 cells, nine-day treatment with BRD7552 dose-dependently increased insulin mRNA expression. In primary human islet cells, three of five donor samples treated with BRD7552 showed significantly dose-dependent induction of PDX1 after 3 or 5 days and of insulin after a 5-day treatment [1]. BRD7552 was capable of inducing the expression of PDX1 in the human PANC-1 ductal cell line.

Chem Biol. 2013 Dec 19;20(12):1513-22.