Leipold1995_ThrombinFormation+inhibitors
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Mathematical model of serine protease inhibition in the tissue factor pathway to thrombin.
- Leipold RJ, Bozarth TA, Racanelli AL, Dicker IB
- The Journal of biological chemistry , 10/ 1995 , Volume 270 , pages: 25383-25387 , PubMed ID: 7592704
- DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0400, USA.
- A mathematical model has been developed to simulate the generation of thrombin by the tissue factor pathway. The model gives reasonable predictions of published experimental results without the adjustment of any parameter values. The model also accounts explicitly for the effects of serine protease inhibitors on thrombin generation. Simulations to define the optimum affinity profile of an inhibitor in this system indicate that for an inhibitor simultaneously potent against VIIa, IXa, and Xa, inhibition of thrombin generation decreases dramatically as the affinity for thrombin increases. Additional simulations show that the reason for this behavior is the sequestration of the inhibitor by small amounts of thrombin generated early in the reaction. This model is also useful for predicting the potency of compounds that inhibit thrombosis in rats. We believe that this is the first mathematical model of blood coagulation that considers the effects of exogenous inhibitors. Such a model, or extensions thereof, should be useful for evaluating targets for therapeutic intervention in the processes of blood coagulation.
Submitter of this revision: Michael Schubert
Modellers: Michael Schubert
Metadata information
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| Name | Description | Size | Actions |
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| MODEL1109150002_url.xml | SBML L2V4 representation of Leipold1995_ThrombinFormation+inhibitors | 85.37 KB | Preview | Download |
Additional files |
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| MODEL1109150002-biopax2.owl | Auto-generated BioPAX (Level 2) | 66.84 KB | Preview | Download |
| MODEL1109150002-biopax3.owl | Auto-generated BioPAX (Level 3) | 129.47 KB | Preview | Download |
| MODEL1109150002.m | Auto-generated Octave file | 23.06 KB | Preview | Download |
| MODEL1109150002.pdf | Auto-generated PDF file | 248.63 KB | Preview | Download |
| MODEL1109150002.png | Auto-generated Reaction graph (PNG) | 648.84 KB | Preview | Download |
| MODEL1109150002.sci | Auto-generated Scilab file | 21.35 KB | Preview | Download |
| MODEL1109150002.svg | Auto-generated Reaction graph (SVG) | 115.70 KB | Preview | Download |
| MODEL1109150002.vcml | Auto-generated VCML file | 574.00 Bytes | Preview | Download |
| MODEL1109150002.xpp | Auto-generated XPP file | 19.14 KB | Preview | Download |
| MODEL1109150002_urn.xml | Auto-generated SBML file with URNs | 95.38 KB | Preview | Download |
- Model originally submitted by : Michael Schubert
- Submitted: Sep 15, 2011 2:26:29 PM
- Last Modified: Sep 15, 2011 2:32:24 PM
Revisions
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Version: 2
- Submitted on: Sep 15, 2011 2:32:24 PM
- Submitted by: Michael Schubert
- With comment: Current version of Leipold1995_ThrombinFormation+inhibitors
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Version: 1
- Submitted on: Sep 15, 2011 2:26:29 PM
- Submitted by: Michael Schubert
- With comment: Original import of Leipold1995_ThrombinFormation+inhibitors
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