A small-molecule inducer of PDX1 expression identified by high-throughput screening

Chem Biol. 2013 Dec 19;20(12):1513-22. doi: 10.1016/j.chembiol.2013.10.013. Epub 2013 Nov 27.


Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor important for both pancreas development and mature β cell function. The ectopic overexpression of Pdx1, Neurog3, and MafA in mice reprograms acinar cells to insulin-producing cells. We developed a quantitative PCR-based gene expression assay to screen more than 60,000 compounds for expression of each of these genes in the human PANC-1 ductal carcinoma cell line. We identified BRD7552, which upregulated PDX1 expression in both primary human islets and ductal cells, and induced epigenetic changes in the PDX1 promoter consistent with transcriptional activation. Prolonged compound treatment induced both insulin mRNA and protein and also enhanced insulin expression induced by the three-gene combination. These results provide a proof of principle for identifying small molecules that induce expression of transcription factors to control cellular reprogramming.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • High-Throughput Screening Assays / methods
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Polymerase Chain Reaction / methods
  • Promoter Regions, Genetic / drug effects
  • Small Molecule Libraries / pharmacology*
  • Trans-Activators / genetics*
  • Transcriptional Activation / drug effects


  • Homeodomain Proteins
  • Small Molecule Libraries
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein