4AJP

Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- 6yl)amino)-3-oxo-propyl)amino)-4-oxo-butyl)phenyl)methyl)propanedioic acid

4AJP の概要

• エントリーDOI: 10.2210/pdb4ajp/pdb
• 関連するPDBエントリー: 1I10 4AJ1 4AJ2 4AJ4 4AJE 4AJH 4AJI 4AJJ 4AJK 4AJL 4AJN 4AJO
• 分子名称: L-LACTATE DEHYDROGENASE A CHAIN, {4-[4-({3-[(2-METHYL-1,3-BENZOTHIAZOL-6-YL)AMINO]-3-OXOPROPYL}AMINO)-4-OXOBUTYL]BENZYL}PROPANEDIOIC ACID, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase-inhibitor complex, fragment based lead generated inhibitors, oxidoreductase/inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: P00338
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 153052.60

構造登録者

Tucker, J.A.,Brassington, C.,Caputo, A.,Ward, R.,Pearson, S.,Watson, M.,Tart, J.,Davies, G. (登録日: 2012-02-16, 公開日: 2012-03-21, 最終更新日: 2023-12-20)

主引用文献

Ward, R.,Brassington, C.,Breeze, A.L.,Caputo, A.,Critchlow, S.,Davies, G.,Goodwin, L.,Hassall, G.,Greenwood, R.,Holdgate, G.,Mrosek, M.,Norman, R.A.,Pearson, S.,Tart, J.,Tucker, J.A.,Vogtherr, M.,Whittaker, D.,Wingfield, J.,Winter, J.,Hudson, K.
The Design and Synthesis of Novel Lactate Dehydrogenase a Inhibitors by Fragment-Based Lead Generation
J.Med.Chem., 55:3285-, 2012

PubMed Abstract: Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

PubMed: 22417091
DOI: 10.1021/JM201734R

実験手法

X-RAY DIFFRACTION (2.38 Å)