Use of cell-based screening to identify small-molecule compounds that modulate claudin-4 expression

Claudins constitute a family of at least 27 proteins with four transmembrane domains, and play a pivotal role in maintaining tight-junctions seals in diverse epithelial tissues. The expression of claudin-4 often changes in intestinal tissues of inflammatory bowel disease and various human cancers. Therefore, claudin-4 is a promising target for treatment of these diseases. In our previous study, we established a reporter cell line to monitor claudin-4 expression on the basis of a functional claudin-4 promoter. Using this cell line, we have performed a cell-based screen of a library contg. 2642 biol. active small-mol. compds. to identify modulators of claudin-4 expression. The screen identified 24 potential modulators of the claudin-4 promoter activity. Fourteen of these compds. (12 of them novel) induced endogenous claudin-4 expression. The identified compds. might serve as lead compds. targeting aberrant gene expression in inflammatory bowel disease. [on SciFinder(R)]