Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15099-104. doi: 10.1073/pnas.1010018107. Epub 2010 Aug 9.
High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused alpha-cells to adopt several morphological and gene expression features of a beta-cell state. Assay-performance profile analysis suggests kinase inhibition as a mechanism of action, and we show that biochemical and cellular inhibition of the RSK kinase family by BRD7389 is likely related to its ability induce a beta-cell-like state. BRD7389 also increases the endocrine cell content and function of donor human pancreatic islets in culture.
高内涵筛选小分子胰岛素诱导物鉴定出化合物 BRD7389，它使 alpha 细胞呈现出几种 beta 细胞状态的形态和基因表达特征。分析表明该化合物的作用机制可能是抑制激酶，我们还证明 BRD7389 通过抑制 RSK 激酶家族的生化和细胞活性与其诱导 beta 样细胞状态的能力有关。BRD7389 还能增加培养物中供体人胰岛内分泌细胞的含量和功能。
