Background:

IC50: 30, 119, 83, 4, and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8, respectively.

MS023 is a type I PRMTs inhibitor.

Protein arginine methyltransferases (PRMTs) play a critical role in various biological processes. PRMT overexpression has been observed in a variety of human diseases including cancer. PRMTs has been divided into three categories: type I PRMTs for catalyzing mono- and asymmetric dimethylation of arginine residues, type II PRMTs for catalyzing mono- and symmetric dimethylation of arginine residues, and type III PRMT for catalyzing only monomethylation of arginine residues.

In vitro: Previous study showed that MS023 had excellent potency for type I PRMTs but was completely inactive to both type II and type III PRMTs, protein lysine methyltransferases as well as DNA methyltransferases. Moreover, the crystal structure of PRMT6 with MS023 indicated that MS023 bound to the substrate binding site. In addition, MS023 could potently decrease the cellular levels of histone arginine asymmetric dimethylation. Furthermore, MS023 could reduce the levels of arginine asymmetric dimethylation and could also concurrently increase the cellular levels of both arginine monomethylation and symmetric dimethylation [1].

In vivo: So far, there is no animal in vivo data reported.

Clinical trial: Up to now, MS023 is still in the preclinical development stage.

Reference:
[1] Eram MS, et al.  A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chem Biol. 2016 Mar 18;11(3):772-81.