3OQ1

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

Summary for 3OQ1

• Entry DOI: 10.2210/pdb3oq1/pdb
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 3-(2-fluoroethyl)-4-({4-[(2S)-1,1,1-trifluoro-2-hydroxypropan-2-yl]phenyl}sulfonyl)benzonitrile, ... (4 entities in total)
• Functional Keywords: oxidoreductase, 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: 4
• Total formula weight: 131926.62

Authors

Wang, Z.,Sudom, A.,Walker, N.P. (deposition date: 2010-09-02, release date: 2011-07-20, Last modification date: 2024-02-21)

Primary citation

Yan, X.,Wang, Z.,Sudom, A.,Cardozo, M.,DeGraffenreid, M.,Di, Y.,Fan, P.,He, X.,Jaen, J.C.,Labelle, M.,Liu, J.,Ma, J.,McMinn, D.,Miao, S.,Sun, D.,Tang, L.,Tu, H.,Ursu, S.,Walker, N.,Ye, Q.,Powers, J.P.
The synthesis and SAR of novel diarylsulfone 11beta-HSD1 inhibitors
Bioorg.Med.Chem.Lett., 20:7071-7075, 2010

PubMed Abstract: In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.

PubMed: 20971000
DOI: 10.1016/j.bmcl.2010.09.097

Experimental method

X-RAY DIFFRACTION (2.6 Å)