Exploring the efficiency of thrombin inhibitors with a quantitative model of the coagulation cascade

FEBS Letters

article

Elena G. Zavyalova¹  Nikita B. Ustinov¹  Alexey M. Kopylov¹ 

[1] Chemistry Department, Lomonosov Moscow State University

关键词: anticoagulant;    coagulation cascade;    enzyme;    kinetics;    mathematical modeling;   

DOI  :  10.1002/1873-3468.13684

来源: John Wiley & Sons Ltd.

【 摘 要 】

A detailed mathematical description of the coagulation cascade is a challenging task due to a huge set of protein–protein interactions. Simplified models do not permit quantitative description of anticoagulants. The detailed mathematical model presented here was constructed with 98 reactions between 70 species. The model was verified using experimental data on thrombin generation. Four thrombin inhibitors, which have different inhibitory mechanisms, were incorporated into the model. All four thrombin inhibitors delayed prothrombin conversion into thrombin, but did not preclude it. At high inhibitor concentration, thrombin-mediated positive feedback loops were strongly inhibited and the proportion of prothrombin, converted with factor Xa only, was considerably increased. The most potent inhibitor of prothrombin conversion was aptamer NU172, which also binds prothrombin and inhibits its conversion.

【 授权许可】

Unknown