3KM4

Optimization of Orally Bioavailable Alkyl Amine Renin Inhibitors

3KM4 の概要

• エントリーDOI: 10.2210/pdb3km4/pdb
• 関連するPDBエントリー: 3D91 3GW5
• 分子名称: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, (3R)-3-[(1S)-4-(acetylamino)-1-(3-chlorophenyl)-1-hydroxybutyl]-N-{(1S)-2-cyclohexyl-1-[(methylamino)methyl]ethyl}piperidine-1-carboxamide, ... (5 entities in total)
• 機能のキーワード: renin, aspartate protease, hypertension, renin expression, renin inhibitor, aspartyl protease, cleavage on pair of basic residues, disulfide bond, glycoprotein, hydrolase, protease, secreted, 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: 76609.34

構造登録者

Wu, Z.,McKeever, B.M. (登録日: 2009-11-09, 公開日: 2010-01-12, 最終更新日: 2024-11-06)

主引用文献

Xu, Z.,Cacatian, S.,Yuan, J.,Simpson, R.D.,Jia, L.,Zhao, W.,Tice, C.M.,Flaherty, P.T.,Guo, J.,Ishchenko, A.,Singh, S.B.,Wu, Z.,McKeever, B.M.,Scott, B.B.,Bukhtiyarov, Y.,Berbaum, J.,Mason, J.,Panemangalore, R.,Cappiello, M.G.,Bentley, R.,Doe, C.P.,Harrison, R.K.,McGeehan, G.M.,Dillard, L.W.,Baldwin, J.J.,Claremon, D.A.
Optimization of orally bioavailable alkyl amine renin inhibitors.
Bioorg.Med.Chem.Lett., 20:694-699, 2010

PubMed Abstract: Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.

PubMed: 19959358
DOI: 10.1016/j.bmcl.2009.11.066

実験手法

X-RAY DIFFRACTION (1.9 Å)