title: A novel arginine methyltransferase inhibitor with cellular activity.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spannhoff
authors.forename: Rospita
authors.initials: R
authors.lastname: Machmur
authors.forename: Ralf
authors.initials: R
authors.lastname: Heinke
authors.forename: Patrick
authors.initials: P
authors.lastname: Trojer
authors.forename: Ingo
authors.initials: I
authors.lastname: Bauer
authors.forename: Gerald
authors.initials: G
authors.lastname: Brosch
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hanefeld
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: 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
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases