2b7d: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2b7d.gif|left|200px]] | [[Image:2b7d.gif|left|200px]] | ||
'''Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model''' | {{Structure | ||
|PDB= 2b7d |SIZE=350|CAPTION= <scene name='initialview01'>2b7d</scene>, resolution 2.24Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=C1B:(2R)-2-[5-(5-CARBAMIMIDOYL-1H-BENZOIMIDAZOL-2-YL)-6,2'-DIHYDROXY-5'-UREIDOMETHYL-BIPHENYL-3-YL]-SUCCINIC ACID'>C1B</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] | |||
|GENE= F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model''' | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
2B7D is a [ | 2B7D 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=2B7D OCA]. | ||
==Reference== | ==Reference== | ||
Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model., Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:[http:// | Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model., Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16412633 16412633] | ||
[[Category: Coagulation factor VIIa]] | [[Category: Coagulation factor VIIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 37: | Line 46: | ||
[[Category: short hydrogen bond]] | [[Category: short hydrogen bond]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:58:24 2008'' | ||
Revision as of 16:58, 20 March 2008
| |||||||
| , resolution 2.24Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | F7 (Homo sapiens), F3 (Homo sapiens) | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this StructureAbout this Structure
2B7D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model., Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:16412633
Page seeded by OCA on Thu Mar 20 15:58:24 2008