3FRJ

Crystal Structure of 11b-Hydroxysteroid Dehydrogenase-1 (11b-HSD1) in Complex with Piperidyl Benzamide Inhibitor

3FRJ の概要

• エントリーDOI: 10.2210/pdb3frj/pdb
• 分子名称: Corticosteroid 11-beta-Dehydrogenase, Isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, N-{1-[(1-carbamoylcyclopropyl)methyl]piperidin-4-yl}-N-cyclopropyl-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamide, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, endoplasmic reticulum, glycoprotein, lipid metabolism, membrane, 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: 2
• 化学式量合計: 65614.06

構造登録者

Wang, Z.,Sudom, A.,Walker, N.P. (登録日: 2009-01-08, 公開日: 2009-06-16, 最終更新日: 2024-02-21)

主引用文献

Rew, Y.,McMinn, D.L.,Wang, Z.,He, X.,Hungate, R.W.,Jaen, J.C.,Sudom, A.,Sun, D.,Tu, H.,Ursu, S.,Villemure, E.,Walker, N.P.,Yan, X.,Ye, Q.,Powers, J.P.
Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors.
Bioorg.Med.Chem.Lett., 19:1797-1801, 2009

PubMed Abstract: Discovery and optimization of a piperidyl benzamide series of 11beta-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives.

PubMed: 19217779
DOI: 10.1016/j.bmcl.2009.01.058

実験手法

X-RAY DIFFRACTION (2.3 Å)