title: Small Molecule Inhibitors of Protein Arginine Methyltransferases.
abstract: BACKGROUND
  Arginine methylation is an abundant posttranslational modification occurring in mammalian cells and catalyzed by protein arginine methyltransferases (PRMTs). Misregulation and aberrant expression of PRMTs are associated with various disease states, notably cancer. PRMTs are prominent therapeutic targets in drug discovery.
  
  
  METHODS
  The authors provide an updated review of the research on the development of chemical modulators for PRMTs. Great efforts are seen in screening and designing potent and selective PRMT inhibitors, and a number of micromolar and submicromolar inhibitors have been obtained for key PRMT enzymes such as PRMT1, CARM1, and PRMT5. The authors provide a focus on their chemical structures, mechanism of action, and pharmacological activities. Pros and cons of each type of inhibitors are also discussed.
  
  
  CONCLUSIONS
  Several key challenging issues exist in PRMT inhibitor discovery. Structural mechanisms of many PRMT inhibitors remain unclear. There lacks consistency in potency data due to divergence of assay methods and conditions. Physiologically relevant cellular assays are warranted. Substantial engagements are needed to investigate pharmacodynamics and pharmacokinetics of the new PRMT inhibitors in pertinent disease models. Discovery and evaluation of potent, isoform-selective, cell-permeable and in vivo-active PRMT modulators will continue to be an active arena of research in years ahead.
authors.affiliation: a Department of Pharmaceutical and Biomedical Sciences , The University of Georgia , Athens , GA , USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: a Department of Pharmaceutical and Biomedical Sciences , The University of Georgia , Athens , GA , USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.affiliation: b Institute of Biological Chemistry , Academia Sinica , Nankang , Taipei , Taiwan.
authors.forename: Meng-Chiao
authors.initials: MC
authors.lastname: Ho
authors.affiliation: a Department of Pharmaceutical and Biomedical Sciences , The University of Georgia , Athens , GA , USA.
authors.forename: Y George
authors.initials: YG
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D011484:Protein-Arginine N-Methyltransferases
keywords: Arginine methylation; Chemical probe; Drug discovery; Epigenetics; Histone methylation; Inhibitor; PRMT