3CWE

PTP1B in complex with a phosphonic acid inhibitor

3CWE の概要

• エントリーDOI: 10.2210/pdb3cwe/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 1, MAGNESIUM ION, [{2-bromo-4-[(2R)-3-oxo-2,3-diphenylpropyl]phenyl}(difluoro)methyl]phosphonic acid, ... (4 entities in total)
• 機能のキーワード: phosphatase, phosphonates, diabetes, inhibitor, acetylation, endoplasmic reticulum, hydrolase, membrane, oxidation, phosphoprotein, polymorphism, protein phosphatase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P18031
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34277.80

構造登録者

Scapin, G.,Han, Y.,Kennedy, B.P. (登録日: 2008-04-21, 公開日: 2008-06-10, 最終更新日: 2024-02-21)

主引用文献

Han, Y.,Belley, M.,Bayly, C.I.,Colucci, J.,Dufresne, C.,Giroux, A.,Lau, C.K.,Leblanc, Y.,McKay, D.,Therien, M.,Wilson, M.C.,Skorey, K.,Chan, C.C.,Scapin, G.,Kennedy, B.P.
Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor
Bioorg.Med.Chem.Lett., 18:3200-3205, 2008

PubMed Abstract: A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and cancer.

PubMed: 18477508
DOI: 10.1016/j.bmcl.2008.04.064

実験手法

X-RAY DIFFRACTION (1.6 Å)