We discovered potent small molecule inhibitors against the WIN site of WDR5. These inhibitors selectively block the proliferation of mammalian cells carrying fusions of the MLL1 oncogene. Here, we show that these inhibitors result in the rapid displacement of WDR5 from chromatin in both sensitive (MV4:11) and non-sensitive (K562) cell lines, induce early changes in the distribution of active polymerases at a subset of WDR5-bound genes, and induce global transcript changes that are consistent with induction of the tumor suppressor p53. SOURCE: Qi Liu (qi.liu@vanderbilt.edu) -  Vanderbilt University Medical Center

Pluto Bioinformatics

GSE115377: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomolar affinity