Nava Salman-Kesner

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

Introduction https://www.youtube.com/watch?v=cy3a__OOa2M

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

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

Objectives

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

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

Results

Results

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

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

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

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

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.

Acknowledgement

Thank you