3PDJ

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with 4,4-Disubstituted Cyclohexylbenzamide Inhibitor

Summary for 3PDJ

• Entry DOI: 10.2210/pdb3pdj/pdb
• Related: 3BZU 3CZR 3D3E 3D4N 3D5Q 3FCO 3FRJ
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, N-[trans-4-(3-amino-3-oxopropyl)-4-phenylcyclohexyl]-N-cyclopropyl-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamide, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• Functional Keywords: 11beta, hydroxysteroid, dehydrogenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 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: 62705.91

Authors

Wang, Z.,Sudom, A.,Walker, N.P. (deposition date: 2010-10-22, release date: 2011-10-05, Last modification date: 2024-02-21)

Primary citation

Sun, D.,Wang, Z.,Caille, S.,DeGraffenreid, M.,Gonzalez-Lopez de Turiso, F.,Hungate, R.,Jaen, J.C.,Jiang, B.,Julian, L.D.,Kelly, R.,McMinn, D.L.,Kaizerman, J.,Rew, Y.,Sudom, A.,Tu, H.,Ursu, S.,Walker, N.,Willcockson, M.,Yan, X.,Ye, Q.,Powers, J.P.
Synthesis and Optimization of Novel 4,4-Disubstituted Cyclohexylbenzamide Derivatives as Potent 11beta-HSD1 Inhibitors
Bioorg.Med.Chem.Lett., 21:405-410, 2011

PubMed Abstract: The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.

PubMed: 21093258
DOI: 10.1016/j.bmcl.2010.10.129

Experimental method

X-RAY DIFFRACTION (2.3 Å)