2IRW

Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) with NADP and Adamantane Ether Inhibitor

Summary for 2IRW

• Entry DOI: 10.2210/pdb2irw/pdb
• Related: 2ILT
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (1S,3R,4S,5S,7S)-4-{[2-(4-METHOXYPHENOXY)-2-METHYLPROPANOYL]AMINO}ADAMANTANE-1-CARBOXAMIDE (3 entities in total)
• Functional Keywords: hsd1, nadp, inhibitor, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : P28845
• Total number of polymer chains: 8
• Total formula weight: 241365.54

Authors

Longenecker, K.L.,Patel, J.R.,Russell, J.,Qin, W. (deposition date: 2006-10-16, release date: 2007-01-23, Last modification date: 2024-02-21)

Primary citation

Patel, J.R.,Shuai, Q.,Dinges, J.,Winn, M.,Pliushchev, M.,Fung, S.,Monzon, K.,Chiou, W.,Wang, J.,Pan, L.,Wagaw, S.,Engstrom, K.,Kerdesky, F.A.,Longenecker, K.,Judge, R.,Qin, W.,Imade, H.M.,Stolarik, D.,Beno, D.W.,Brune, M.,Chovan, L.E.,Sham, H.L.,Jacobson, P.,Link, J.T.
Discovery of adamantane ethers as inhibitors of 11beta-HSD-1: Synthesis and biological evaluation.
Bioorg.Med.Chem.Lett., 17:750-755, 2007

PubMed Abstract: A novel class of adamantane ethers 11beta-hydroxysteroid hydrogenase type I inhibitors has been discovered. These compounds have excellent HSD-1 potency and selectivity against HSD-2. The structure-activity relationships, selectivity, metabolism, PK, ex vivo pharmacodynamic data, and an X-ray crystal structure of one of these inhibitors bound to h-HSD-1 are discussed.

PubMed: 17110106
DOI: 10.1016/j.bmcl.2006.10.074

Experimental method

X-RAY DIFFRACTION (3.1 Å)