2ANK

orally active thrombin inhibitors in complex with thrombin and an exosite decapeptide

2ANK の概要

• エントリーDOI: 10.2210/pdb2ank/pdb
• 関連するPDBエントリー: 2A2X
• 関連するBIRD辞書のPRD_ID: PRD_000480
• 分子名称: Thrombin heavy chain, Thrombin light chain, synthetic peptide, ... (5 entities in total)
• 機能のキーワード: blood clotting, hydrolase, serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35615.66

構造登録者

Lange, U.E.W.,Baucke, D.,Hornberger, W.,Mack, H.,Seitz, W.,Hoeffken, H.W. (登録日: 2005-08-11, 公開日: 2006-11-14, 最終更新日: 2023-08-23)

主引用文献

Lange, U.E.W.,Baucke, D.,Hornberger, W.,Mack, H.,Seitz, W.,Hoeffken, H.W.
Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety
BIOORG.MED.CHEM.LETT., 16:2648-2653, 2006

PubMed Abstract: Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration.

PubMed: 16460939
DOI: 10.1016/j.bmcl.2006.01.046

実験手法

X-RAY DIFFRACTION (2.46 Å)