3D4N

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Sulfonamide Inhibitor

3D4N の概要

• エントリーDOI: 10.2210/pdb3d4n/pdb
• 関連するPDBエントリー: 3CZR 3D3E
• 分子名称: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1-{[(3R)-3-methyl-4-({4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]phenyl}sulfonyl)piperazin-1-yl]methyl}cyclopropanecarboxamide, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, 11beta, hydroxysteroid, dehydrogenase, endoplasmic reticulum, glycoprotein, lipid metabolism, membrane, microsome, nadp, polymorphism, signal-anchor, steroid metabolism, transmembrane
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type II membrane protein: P28845
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132119.07

構造登録者

Wang, Z.,Liu, J.,Sudom, A.,Walker, N.P. (登録日: 2008-05-14, 公開日: 2008-07-22, 最終更新日: 2024-02-21)

主引用文献

Julian, L.D.,Wang, Z.,Bostick, T.,Caille, S.,Choi, R.,Degraffenreid, M.,Di, Y.,He, X.,Hungate, R.W.,Jaen, J.C.,Liu, J.,Monshouwer, M.,McMinn, D.,Rew, Y.,Sudom, A.,Sun, D.,Tu, H.,Ursu, S.,Walker, N.,Yan, X.,Ye, Q.,Powers, J.P.
Discovery of Novel, Potent Benzamide Inhibitors of 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model
J.Med.Chem., 51:3953-3960, 2008

PubMed Abstract: We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.

PubMed: 18553955
DOI: 10.1021/jm800310g

実験手法

X-RAY DIFFRACTION (2.5 Å)