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

3CH6 の概要

• エントリーDOI: 10.2210/pdb3ch6/pdb
• 分子名称: 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)
• 機能のキーワード: 11b-hsd1, sdr, dehydrogenase, hydroxysteroid, inhibitor, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : P28845
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 129664.64

構造登録者

Sheriff, S. (登録日: 2008-03-07, 公開日: 2008-06-10, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.35 Å)