2NT7

Crystal structure of PTP1B-inhibitor complex

2NT7 の概要

• エントリーDOI: 10.2210/pdb2nt7/pdb
• 関連するPDBエントリー: 2H4G 2H4K 2HCE 2HCW 2HCX 2HFA 2NTA
• 分子名称: Tyrosine-protein phosphatase non-receptor type 1, {[5-(3-{[1-(BENZYLSULFONYL)PIPERIDIN-4-YL]AMINO}PHENYL)-4-BROMO-2-(2H-TETRAZOL-5-YL)-3-THIENYL]OXY}ACETIC ACID (3 entities in total)
• 機能のキーワード: ptp1b, protein-inhibitor complex, hydrolase
• 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: 35453.23

構造登録者

Xu, W.,Follows, B. (登録日: 2006-11-07, 公開日: 2007-04-17, 最終更新日: 2023-12-27)

主引用文献

Wan, Z.K.,Follows, B.,Kirincich, S.,Wilson, D.,Binnun, E.,Xu, W.,Joseph-McCarthy, D.,Wu, J.,Smith, M.,Zhang, Y.L.,Tam, M.,Erbe, D.,Tam, S.,Saiah, E.,Lee, J.
Probing acid replacements of thiophene PTP1B inhibitors.
Bioorg.Med.Chem.Lett., 17:2913-2920, 2007

PubMed Abstract: The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B.

PubMed: 17336064
DOI: 10.1016/j.bmcl.2007.02.043

実験手法

X-RAY DIFFRACTION (2.1 Å)