Small Molecule Inhibitors of Protein Arginine Methyltransferases

Introduction: Arginine methylation is definitely an abundant posttranslational modification occurring in mammalian cells and catalyzed by protein arginine methyltransferases (PRMTs). Misregulation and aberrant expression of PRMTs are connected with assorted disease states, particularly cancer. PRMTs are prominent therapeutic targets in drug discovery.

Areas covered: The authors offer an updated overview of the study on the introduction of chemical modulators for PRMTs. Great attempts are observed in screening and designing potent and selective PRMT inhibitors, and numerous micromolar and submicromolar inhibitors happen to be acquired for key PRMT enzymes for example PRMT1, CARM1, and PRMT5. The authors give a concentrate on their chemical structures, mechanism of action, and medicinal activities. Benefits and drawbacks of every kind of inhibitors will also be discussed.

Expert opinion: Several key challenging issues appear in PRMT inhibitor discovery. Structural mechanisms of numerous PRMT inhibitors remain unclear. There lacks consistency in potency data because of divergence of assay methods and types of conditions. Physiologically relevant cellular assays are warranted. Substantial engagements are necessary to investigate pharmacodynamics and pharmacokinetics from the new PRMT inhibitors in pertinent disease models. Discovery and look at potent, isoform-selective, cell-permeable as well as in vivo-active PRMT modulators will still be an energetic whole world of research in a long time MRTX1719 ahead.