Protein arginine methyltransferase 1, 3, 4, and 6 (PRMT1/3/4/6)

Protein arginine methyltransferase 1, 3, 4, and 6 (PRMT1/3/4/6) are key enzymes within the Type I PRMT family that catalyze the asymmetric dimethylation of arginine residues on both histone and non-histone proteins [3, 11, 15]. These enzymes are essential regulators of fundamental cellular processes, including gene transcription, RNA splicing, and the DNA damage response [6, 10, 13]. Dysregulation or overexpression of these PRMTs is frequently observed in various human malignancies, such as lung, breast, and hematological cancers, where they drive oncogenic pathways that support tumor cell proliferation, survival, and therapeutic resistance [1, 15, 19]. Consequently, PRMT1/3/4/6 have emerged as significant therapeutic targets, leading to the development of several small-molecule inhibitors designed to disrupt their catalytic activity [2, 8, 12]. While preclinical studies have shown robust anti-tumor efficacy, clinical progress has been tempered by safety concerns, most notably the risk of thromboembolic events observed in early-phase trials for certain inhibitors [1, 4, 12].

Other names

Type I Protein Arginine MethyltransferasesPRMT1PRMT3PRMT4PRMT6CARM1 (Coactivator-associated arginine methyltransferase 1)Protein arginine N-methyltransferase 1Protein arginine N-methyltransferase 3Protein arginine N-methyltransferase 4Protein arginine N-methyltransferase 6

Inhibition of protein arginine methyltransferase activity by competing with the substrate or the methyl donor S-adenosyl-L-methionine (SAM), thereby reducing asymmetric dimethylation of arginine residues [8, 11, 19].