4UY1

Novel pyrazole series of group X Secretory Phospholipase A2 (sPLA2-X) inhibitors

4UY1 の概要

• エントリーDOI: 10.2210/pdb4uy1/pdb
• 分子名称: GROUP 10 SECRETORY PHOSPHOLIPASE A2, CALCIUM ION, PENTAETHYLENE GLYCOL, ... (7 entities in total)
• 機能のキーワード: hydrolase, fragment based lead generation, virtual screening, drug discovery
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted : O15496
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31274.07

構造登録者

Sandmark, J.,Oster, L.,Hallberg, K.,Bodin, C.,Chen, H. (登録日: 2014-08-28, 公開日: 2014-10-15, 最終更新日: 2024-10-23)

主引用文献

Chen, H.,Knerr, L.,Akerud, T.,Hallberg, K.,Bodin, C.,Oster, L.,Rohman, M.,Osterlund, K.,Beisel, H.G.,Olsson, T.,Brengdhal, J.,Sandmark, J.
Discovery of a Novel Pyrazole Series of Group X Secreted Phospholipase A2 Inhibitor (Spla2X) Via Fragment Based Virtual Screening
Bioorg.Med.Chem.Lett., 24:5251-, 2014

PubMed Abstract: The discovery of potent novel pyrazole containing group X secreted phospholipase A2 inhibitors via structure based virtual screening is reported. Docking was applied on a large set of in-house fragment collection and pharmacophore feature matching was used to filter docking poses. The selected virtual screening hits was run in NMR screening, a potent pyrazole containing fragment hit was identified and confirmed by its complex X-ray structure and the following biochemical assay result. Expansion on the fragment hit has led to further improvement of potency while maintaining high ligand efficiency, thus supporting the further development of this chemical series.

PubMed: 25316315
DOI: 10.1016/J.BMCL.2014.09.058

実験手法

X-RAY DIFFRACTION (2.2 Å)