3CH6

Crystal Structure of 11beta-HSD1 Double Mutant (L262R, F278E) Complexed with (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone

Summary for 3CH6

• Entry DOI: 10.2210/pdb3ch6/pdb
• Descriptor: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone, ... (4 entities in total)
• Functional Keywords: 11b-hsd1, sdr, dehydrogenase, hydroxysteroid, inhibitor, oxidoreductase
• 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: 129664.64

Authors

Sheriff, S. (deposition date: 2008-03-07, release date: 2008-06-10, Last modification date: 2024-04-03)

Primary citation

Wang, H.,Ruan, Z.,Li, J.J.,Simpkins, L.M.,Smirk, R.A.,Wu, S.C.,Hutchins, R.D.,Nirschl, D.S.,Van Kirk, K.,Cooper, C.B.,Sutton, J.C.,Ma, Z.,Golla, R.,Seethala, R.,Salyan, M.E.,Nayeem, A.,Krystek, S.R.,Sheriff, S.,Camac, D.M.,Morin, P.E.,Carpenter, B.,Robl, J.A.,Zahler, R.,Gordon, D.A.,Hamann, L.G.
Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1
Bioorg.Med.Chem.Lett., 18:3168-3172, 2008

PubMed Abstract: Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series.

PubMed: 18485702
DOI: 10.1016/j.bmcl.2008.04.069

Experimental method

X-RAY DIFFRACTION (2.35 Å)