3FCO

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

Summary for 3FCO

• Entry DOI: 10.2210/pdb3fco/pdb
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, N-cyclopropyl-N-(cis-4-cyclopropyl-4-hydroxycyclohexyl)-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: 65983.48

Authors

Wang, Z.,Sudom, A.,Walker, N.P. (deposition date: 2008-11-21, release date: 2009-12-01, Last modification date: 2023-12-27)

Primary citation

McMinn, D.L.,Rew, Y.,Sudom, A.,Caille, S.,Degraffenreid, M.,He, X.,Hungate, R.,Jiang, B.,Jaen, J.,Julian, L.D.,Kaizerman, J.,Novak, P.,Sun, D.,Tu, H.,Ursu, S.,Walker, N.P.,Yan, X.,Ye, Q.,Wang, Z.,Powers, J.P.
Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.
Bioorg.Med.Chem.Lett., 19:1446-1450, 2009

PubMed Abstract: Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg).

PubMed: 19185488
DOI: 10.1016/j.bmcl.2009.01.026

Experimental method

X-RAY DIFFRACTION (2.65 Å)