Protein arginine methyltransferases (PRMTs) transfer methyl groups to the arginine residues of histones and other proteins. Fistly, PRMTs add one or two mono-methyl groups to the guanidino nitrogen atoms of arginine residues. And secondly, PRMTs results in epigenetic modification of histones or changes of protein-protein interactions. Lastly, these interactions in turn lead to the regulation of a variety of biological functions. These biological functions include transcriptional activation/repression, signal transduction, cell differentiation, and embryonic development. Moreover, PRMTs catalyze the methylation of a variety of protein substrates, which links to the development, progression and aggressiveness of different types of cancer.
Protein arginine methyltransferase 7 (PRMT7) belongs to the type II methyltransferase capable of generating symmetric dimethyl-arginine (SDMA) modifications of proteins. In addition, PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation. PRMT7 acts as a key mediator of breast cancer metastasis. Moreover, PRMT7 presents the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. PRMT7 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in breast cancer. PRMT7 is a potential target for the therapeutic intervention for highly invasive breast cancers.
Hopefully, SGC3027 is the first potent, selective and cell active chemical probe for PRMT7. Additionally, SGC3027 is a pro-drug, which converts to the active compound SGC8158. SGC3027 binds to PRMT7 with a Kd of <2.5 nM. In cellular assays using C2C12 cells, SGC3027 inhibits the methylation of HSP70 with an IC50 of 1.3 μM.