The Protein Arginine Methyltransferases (PRMTs) are a family of proteins that play important roles in epigenetic modification of genes. They have been found to have crucial roles in various diseases, most notably in cancer. In order to probe their functions and potentials in cancer therapy, we have undertaken efforts to design and discover small-molecule compounds that specifically target PRMT4 and PRMT6. We have also developed a series of functional assays to assess the effects of potential lead compounds on enzymatic activities of PRMT4 and PRMT6 proteins.
We took a computation-facilitated in silico approach to identify small-molecule binders of PRMT4 and to facilitate empirical structure-based design for PRMT6. From these efforts, a few lead compounds have been identified for future studies.
We have established multiple-mode assays for characterizing small molecule’s effects on enzymatic activities of PRMT4 and PRMT6, including biochemical activity assays, cellular activity assay, and downstream-gene regulatory assay.
Our efforts also involved the development of a florescence probe for florescence polarization (FP) assay of PRMT6.