A novel arginine methyltransferase inhibitor with cellular activity
| Autor: | Roland Schüle, Rospita Machmur, Patrick Trojer, Wolfgang Sippl, Ralf Heinke, Manfred Jung, Wolfgang Hanefeld, Astrid Spannhoff, Gerald Brosch, Ingo Bauer |
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| Rok vydání: | 2007 |
| Předmět: |
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Molecular Protein-Arginine N-Methyltransferases Methyltransferase Clinical Biochemistry Pharmaceutical Science Biochemistry Cell Line Drug Discovery Humans Binding site Enzyme Inhibitors Molecular Biology Cofactor binding biology Chemistry Organic Chemistry Intracellular Signaling Peptides and Proteins Biological activity Methyltransferases Amides Enzyme inhibitor Docking (molecular) Histone methyltransferase biology.protein Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(15) |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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