Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases.
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.
Dowden
James
J
School of Chemistry, University Park, University of Nottingham, Nottingham, NG7 2RD, UK. james.dowden@nottingham.ac.uk
Hong
Wei
W
Parry
Richard V
RV
Pike
Richard A
RA
Ward
Stephen G
SG
D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013379:Substrate Specificity
D012097:Repressor Proteins; D012436:S-Adenosylmethionine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human