A novel arginine methyltransferase inhibitor with cellular activity.
Via virtual screening we identified a thioglycolic amide as an arginine methyltransferase (PRMT) inhibitor and tested it and related compounds against the fungal PRMT RmtA and human PRMT1. Compound RM65 was the most potent druglike inhibitor (IC(50)-PRMT1: 55.4 microM) and showed histone hypomethylation in HepG2 cells. Docking studies proposed binding at the substrate and SAM cofactor binding pocket. It may serve as a lead for further PRMT inhibitors useful for the treatment for hormone dependent cancers.
Spannhoff
Astrid
A
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Germany.
Machmur
Rospita
R
Heinke
Ralf
R
Trojer
Patrick
P
Bauer
Ingo
I
Brosch
Gerald
G
Schüle
Roland
R
Hanefeld
Wolfgang
W
Sippl
Wolfgang
W
Jung
Manfred
M
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011484:Protein-Arginine N-Methyltransferases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases