BRD0639 is an inhibitor of the protein-peptide interaction between protein arginine methyltransferase 5 (PRMT5) and PRMT5 binding motif (PBM; IC50 = 13.8 ?M), a conserved peptide motif contained in PRMT5 substrate adaptor proteins (SAPs) that mediates SAP binding to PRMT5.1 It induces the formation of PRMT5 adducts in cells (EC50 = 3 ?M) and disrupts complex formation between PRMT5 and the SAP RIO kinase 1 (RIOK1) in permeabilized cells.
1.McKinney, D.C., McMillan, B.J., Ranaghan, M.J., et al.Discovery of a first-in-class inhibitor of the PRMT5?substrate adaptor interactionJ. Med. Chem.64(15)11148-11168(2022)