1. Nava Salman-Kesner

2. Thromboembolic diseases
Introduction
Thromboembolic diseases
Myocardial infarction, stroke, and deep vein thrombosis
A major cause of morbidity and mortality, particularly in the Western world

3. Introduction

4. Plasminogen activator
Introduction
Clot treatment
Fibrinolytic agents
Anticoagulants
Fibrinolytic agents- breakdown the fibrin inside the clot (tPA, streptokinase, urokinase)
Plasminogen
Plasmin
Plasminogen activator
SK / tPA
Fibrin
Fibrin degradation product

5. Clot treatment Introduction
Anticoagulants- prevent the clot from getting formed
Heparin, Clexane, Rivaroxaban
Coumadin

6. Objectives

7. CADDIS approach (computer-assisted drug discovery)
Methods
CADDIS approach (computer-assisted drug discovery)

8. Genetic algorithm Methods Initialize population Estimation Selection
Crossover and mutation
Is it good enough? No
Yes
Answer

9. Results

10. Results

11. Structures of thrombin inhibitors: 7-8, 8-1, and 8-5
Results
Structures of thrombin inhibitors: 7-8, 8-1, and 8-5

12. Characterization of compound 8-5 derivatives
Results
Characterization of compound 8-5 derivatives

13. Human thrombin- compound 8-5
Results
Human thrombin- compound 8-5
Compound 8-5
Thrombin

14. Elimination of selected compounds from the blood stream
Results
Elimination of selected compounds from the blood stream

15. Conclusion
Starting from a set of 170 randomly chosen compounds, eight design cycles with a total of ~1000 compounds, turned out to be sufficient to identify a novel series of thrombin inhibitors.

16. Acknowledgement

17. Thank you