View source for 2ank

[[Image:2ank.jpg|left|200px]]

 {{Structure
|PDB= 2ank |SIZE=350|CAPTION= <scene name='initialview01'>2ank</scene>, resolution 2.46&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=N12:N-[(1R)-2-[(1-{[({6-[AMINO(IMINO)METHYL]PYRIDIN-3-YL}METHYL)AMINO]CARBONYL}CYCLOPENTYL)AMINO]-1-(CYCLOHEXYLMETHYL)-2-OXOETHYL]GLYCINE'>N12</scene>
|ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] 
|GENE= 
}}

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


==Overview==
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.

==Disease==
Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]]

==About this Structure==
2ANK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANK OCA]. 

==Reference==
Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety., Lange UE, Baucke D, Hornberger W, Mack H, Seitz W, Hoffken HW, Bioorg Med Chem Lett. 2006 May 15;16(10):2648-53. Epub 2006 Feb 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16460939 16460939]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Thrombin]]
[[Category: Baucke, D.]]
[[Category: Hoeffken, H W.]]
[[Category: Hornberger, W.]]
[[Category: Lange, U E.W.]]
[[Category: Mack, H.]]
[[Category: Seitz, W.]]
[[Category: N12]]
[[Category: blood clotting]]
[[Category: hydrolase]]
[[Category: serine protease]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:51:42 2008''