3FRJ

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

Summary for 3FRJ

• Entry DOI: 10.2210/pdb3frj/pdb
• Descriptor: 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)
• Functional Keywords: oxidoreductase, endoplasmic reticulum, glycoprotein, lipid metabolism, membrane, nadp, polymorphism, signal-anchor, steroid metabolism, transmembrane
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Single-pass type II membrane protein: P28845
• Total number of polymer chains: 2
• Total formula weight: 65614.06

Authors

Wang, Z.,Sudom, A.,Walker, N.P. (deposition date: 2009-01-08, release date: 2009-06-16, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)