2B7D

Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model

2B7D の概要

• エントリーDOI: 10.2210/pdb2b7d/pdb
• 分子名称: Coagulation factor VII, Tissue factor, (2R)-2-[5-(5-CARBAMIMIDOYL-1H-BENZOIMIDAZOL-2-YL)-6,2'-DIHYDROXY-5'-UREIDOMETHYL-BIPHENYL-3-YL]-SUCCINIC ACID, ... (5 entities in total)
• 機能のキーワード: short hydrogen bond, blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P08709 P08709; Isoform 1: Membrane ; Single-pass type I membrane protein . Isoform 2: Secreted : P13726
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70422.17

構造登録者

Young, W.B.,Mordenti, J.,Torkelson, S.,Shrader, W.D.,Kolesnikov, A.,Rai, R.,Liu, L.,Hu, H.,Leahy, E.M.,Green, M.J.,Sprengeler, P.A.,Katz, B.A.,Yu, C.,Janc, J.W.,Elrod, K.C.,Marzec, U.M.,Hanson, S.R. (登録日: 2005-10-04, 公開日: 2006-02-14, 最終更新日: 2024-10-16)

主引用文献

Young, W.B.,Mordenti, J.,Torkelson, S.,Shrader, W.D.,Kolesnikov, A.,Rai, R.,Liu, L.,Hu, H.,Leahy, E.M.,Green, M.J.,Sprengeler, P.A.,Katz, B.A.,Yu, C.,Janc, J.W.,Elrod, K.C.,Marzec, U.M.,Hanson, S.R.
Factor VIIa inhibitors: Chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.
Bioorg.Med.Chem.Lett., 16:2037-2041, 2006

PubMed Abstract: Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.

PubMed: 16412633
DOI: 10.1016/j.bmcl.2005.12.059

実験手法

X-RAY DIFFRACTION (2.24 Å)