2ANM

Ternary complex of an orally active thrombin inhibitor with human thrombin and a c-terminal hirudin derived exo-sit inhibitor

Summary for 2ANM

• Entry DOI: 10.2210/pdb2anm/pdb
• Descriptor: thrombin, 2-((R)-1-((S)-2-(N-(6-CARBAMIMIDOYLPYRIDIN-3-YL)METHYLCARBAMOYL)-2H-PYRROL-1(5H)-YL)-3-CYCLOHEXYL-1-OXOPROPAN-2-YLAMINO)ACETIC ACID, ... (4 entities in total)
• Functional Keywords: blood clotting
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734
• Total number of polymer chains: 2
• Total formula weight: 34147.13

Authors

Lange, U.E.W.,Baucke, D.,Hornberger, W.,Mack, H.,Seitz, W.,Hoeffken, H.W. (deposition date: 2005-08-11, release date: 2006-06-13, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)