Protein arginine methyltransferase 6 (PRMT6), a member of type I PRMT enzymes, catalyzes the monomethylation or asymmetric dimethylation of arginine residues. To better understand its biological roles in cells, highly selective inhibitors are needed. The first reported allosteric inhibitor of PRMT6 should fulfill this need. Further comparison with allosteric inhibitors of PRMT5 identified that the dynamics of double-E loop plays a vital role in making this allosteric binding possible.