5ARG

SMYD2 in complex with SGC probe BAY-598

5ARG の概要

• エントリーDOI: 10.2210/pdb5arg/pdb
• 分子名称: N-LYSINE METHYLTRANSFERASE SMYD2, ZINC ION, N-[1-(N'-CYANO-N-[3-(DIFLUOROMETHOXY)PHENYL]CARBAMIMIDOYL)-3-(3,4-DICHLOROPHENYL)-4,5-DIHYDRO-1H-PYRAZOL-4-YL]-N-ETHYL-2-HYDROXYACETAMIDE, ... (6 entities in total)
• 機能のキーワード: transferase, oxidoreductase, methyltransferase, set domain, small molecule inhibitor, sgc probe, drug target
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50898.05

構造登録者

Hillig, R.C.,Badock, V.,Barak, N.,Stellfeld, T.,Eggert, E.,ter Laak, A.,Weiske, J.,Christ, C.D.,Koehr, S.,Stoeckigt, D.,Mowat, J.,Mueller, T.,Fernandez-Montalvan, A.E.,Hartung, I.V.,Stresemann, C.,Brumby, T.,Weinmann, H. (登録日: 2015-09-24, 公開日: 2016-04-27, 最終更新日: 2024-10-23)

主引用文献

Eggert, E.,Hillig, R.C.,Kohr, S.,Stockigt, D.,Weiske, J.,Barak, N.,Mowat, J.,Brumby, T.,Christ, C.D.,Ter Laak, A.,Lang, T.,Fernandez-Montalvan, A.E.,Badock, V.,Weinmann, H.,Hartung, I.V.,Barsyte-Lovejoy, D.,Szewczyk, M.,Kennedy, S.,Li, F.,Vedadi, M.,Brown, P.J.,Santhakumar, V.,Arrowsmith, C.H.,Stellfeld, T.,Stresemann, C.
Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (Bay-598) for the Protein Lysine Methyltransferase Smyd2.
J.Med.Chem., 59:4578-, 2016

PubMed Abstract: Protein lysine methyltransferases have recently emerged as a new target class for the development of inhibitors that modulate gene transcription or signaling pathways. SET and MYND domain containing protein 2 (SMYD2) is a catalytic SET domain containing methyltransferase reported to monomethylate lysine residues on histone and nonhistone proteins. Although several studies have uncovered an important role of SMYD2 in promoting cancer by protein methylation, the biology of SMYD2 is far from being fully understood. Utilization of highly potent and selective chemical probes for target validation has emerged as a concept which circumvents possible limitations of knockdown experiments and, in particular, could result in an improved exploration of drug targets with a complex underlying biology. Here, we report the development of a potent, selective, and cell-active, substrate-competitive inhibitor of SMYD2, which is the first reported inhibitor suitable for in vivo target validation studies in rodents.

PubMed: 27075367
DOI: 10.1021/ACS.JMEDCHEM.5B01890

実験手法

X-RAY DIFFRACTION (1.99 Å)