3Q3T

Alkyl Amine Renin Inhibitors: Filling S1 from S3

3Q3T の概要

• エントリーDOI: 10.2210/pdb3q3t/pdb
• 関連するPDBエントリー: 3GW5 3KM4 3Q4B 3Q5H
• 分子名称: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, [(1S,3R,4S)-3-amino-4-hydroxycyclopentyl]{(3R)-3-[(1S)-1-(biphenyl-2-yl)-1-hydroxy-5-methoxypentyl]piperidin-1-yl}methanone, ... (6 entities in total)
• 機能のキーワード: aspartate protease, hypertension, renin inhibitors, glycoprotein, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P00797
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76325.09

構造登録者

Wu, Z.,McKeever, B. (登録日: 2010-12-22, 公開日: 2011-08-03, 最終更新日: 2024-10-30)

主引用文献

Yuan, J.,Simpson, R.D.,Zhao, W.,Tice, C.M.,Xu, Z.,Cacatian, S.,Jia, L.,Flaherty, P.T.,Guo, J.,Ishchenko, A.,Wu, Z.,McKeever, B.M.,Scott, B.B.,Bukhtiyarov, Y.,Berbaum, J.,Panemangalore, R.,Bentley, R.,Doe, C.P.,Harrison, R.K.,McGeehan, G.M.,Singh, S.B.,Dillard, L.W.,Baldwin, J.J.,Claremon, D.A.
Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket.
Bioorg.Med.Chem.Lett., 21:4836-4843, 2011

PubMed Abstract: Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.

PubMed: 21741239
DOI: 10.1016/j.bmcl.2011.06.043

実験手法

X-RAY DIFFRACTION (2.6 Å)