Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2103-5. doi: 10.1016/j.bmcl.2010.02.069. Epub 2010 Feb 20.

Abstract

Prototype inhibitors of protein arginine methyltransferases (PRMTs) have been constructed by attaching guanidine functionality via a variable linker to non-reactive amine analogues of the cellular co-factor (S)-adenosyl methionine (AdoMet). Potent inhibition of PRMT1 (IC(50) of approximately 3-6 microM) combined with weak inhibition of the lysine methyltransferase SET7 (approximately 50% of activity at 100 microM) was observed for two such compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Methylation
  • Protein-Arginine N-Methyltransferases / antagonists & inhibitors*
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / metabolism
  • S-Adenosylmethionine / analogs & derivatives*
  • S-Adenosylmethionine / pharmacology*
  • Substrate Specificity

Substances

  • Repressor Proteins
  • S-Adenosylmethionine
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • SETD7 protein, human