2b7d: Difference between revisions
New page: left|200px<br /> <applet load="2b7d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b7d, resolution 2.24Å" /> '''Factor VIIa Inhibit... |
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[[Image:2b7d.gif|left|200px]]<br /> | [[Image:2b7d.gif|left|200px]]<br /><applet load="2b7d" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2b7d, resolution 2.24Å" /> | caption="2b7d, resolution 2.24Å" /> | ||
'''Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model'''<br /> | '''Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model'''<br /> | ||
==Overview== | ==Overview== | ||
Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2B7D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with C1B as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | 2B7D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=C1B:'>C1B</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B7D OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Elrod, K | [[Category: Elrod, K C.]] | ||
[[Category: Green, M | [[Category: Green, M J.]] | ||
[[Category: Hanson, S | [[Category: Hanson, S R.]] | ||
[[Category: Hu, H.]] | [[Category: Hu, H.]] | ||
[[Category: Janc, J | [[Category: Janc, J W.]] | ||
[[Category: Katz, B | [[Category: Katz, B A.]] | ||
[[Category: Kolesnikov, A.]] | [[Category: Kolesnikov, A.]] | ||
[[Category: Leahy, E | [[Category: Leahy, E M.]] | ||
[[Category: Liu, L.]] | [[Category: Liu, L.]] | ||
[[Category: Marzec, U | [[Category: Marzec, U M.]] | ||
[[Category: Mordenti, J.]] | [[Category: Mordenti, J.]] | ||
[[Category: Rai, R.]] | [[Category: Rai, R.]] | ||
[[Category: Shrader, W | [[Category: Shrader, W D.]] | ||
[[Category: Sprengeler, P | [[Category: Sprengeler, P A.]] | ||
[[Category: Torkelson, S.]] | [[Category: Torkelson, S.]] | ||
[[Category: Young, W | [[Category: Young, W B.]] | ||
[[Category: Yu, C.]] | [[Category: Yu, C.]] | ||
[[Category: C1B]] | [[Category: C1B]] | ||
[[Category: short hydrogen bond]] | [[Category: short hydrogen bond]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:34:53 2008'' | ||
Revision as of 17:34, 21 February 2008
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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 with as ligand. Active as Coagulation factor VIIa, with EC number 3.4.21.21 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
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