3TFQ

Crystal structure of 11b-hsd1 double mutant (l262r, f278e) complexed with 8-{[(2-CYANOPYRIDIN-3-YL)METHYL]SULFANYL}-6-HYDROXY-3,4-DIHYDRO-1H-PYRANO[3,4-C]PYRIDINE-5-CARBONITRILE

3TFQ の概要

• エントリーDOI: 10.2210/pdb3tfq/pdb
• 関連するPDBエントリー: 3CH6
• 分子名称: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 8-{[(2-cyanopyridin-3-yl)methyl]sulfanyl}-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile, ... (5 entities in total)
• 機能のキーワード: 11b-hsd1, sdr, dehydrogenase, hydroxysteroid, inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 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: 129748.53

構造登録者

Sheriff, S. (登録日: 2011-08-16, 公開日: 2011-11-02, 最終更新日: 2024-04-03)

主引用文献

Wu, S.C.,Yoon, D.,Chin, J.,van Kirk, K.,Seethala, R.,Golla, R.,He, B.,Harrity, T.,Kunselman, L.K.,Morgan, N.N.,Ponticiello, R.P.,Taylor, J.R.,Zebo, R.,Harper, T.W.,Li, W.,Wang, M.,Zhang, L.,Sleczka, B.G.,Nayeem, A.,Sheriff, S.,Camac, D.M.,Morin, P.E.,Everlof, J.G.,Li, Y.X.,Ferraro, C.A.,Kieltyka, K.,Shou, W.,Vath, M.B.,Zvyaga, T.A.,Gordon, D.A.,Robl, J.A.
Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11beta-hydroxydehydrogenase 1 (11beta-HSD1)
Bioorg.Med.Chem.Lett., 21:6693-6698, 2011

PubMed Abstract: Derived from the HTS hit 1, a series of hydroxyisoquinolines was discovered as potent and selective 11β-HSD1 inhibitors with good cross species activity. Optimization of substituents at the 1 and 4 positions of the isoquinoline group in addition to the core modifications, with a special focus on enhancing metabolic stability and aqueous solubility, resulted in the identification of several compounds as potent advanced leads.

PubMed: 21983444
DOI: 10.1016/j.bmcl.2011.09.058

実験手法

X-RAY DIFFRACTION (1.8 Å)