The formation of the proteolytic complex composed of the serine protease Factor VIIa and the cell-associated glycoprotein tissue factor (FVIIa/TF) initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. The critical role of the coagulation cascade in pathological thrombosis has been the basis for significant efforts to design selective inhibitors of the prot...

Serine proteases (SP), such as thrombin, factor Xa, elastase, trypsin are implicated in many clinical disorders such as emphysema, arthritis and cardiovascular diseases. These enzymes, in normal physiological conditions, are regulated by naturally occurring serine protease inhibitors, such as anti-thrombin III involved in thromb in inhibition. Primitive parasitic invertebrates have co-evolved h...

The serine protease thrombin is the effector enzyme of blood coagulation. It has many activities critical for the formation of stable clots, including cleavage of fibrinogen to fibrin, activation of platelets and conversion of procofactors to active cofactors. Thrombin carries-out its multiple functions by utilising three special features: a deep active site cleft and two anion binding exosites...

In contrast to heparins and oral anticoagulants, anti IIa inhibitors (thrombin inhibitors) are able to directly inhibit the protease activity of thrombin and can thereby precisely control the blood coagulation process. Direct thrombin inhibitors are either biosimilars (r-hirudin) or synthetically produced substances (bivalirudin, argatroban, dabigatran). In 1997 r-hirudin was introduced into cl...

Thromboembolic disease is caused by improper functioning of the blood coagulation process. The serine protease Factor Xa plays a central role in the coagulation cascade. FXa inhibitors have been identified to maintain a patient’s blood level within the therapeutic range and also shown to activate clotting over a much wider concentration range than thrombin in invitro assays. Predicting the bind...

The formation of the proteolytic complex composed of the serine protease Factor VIIa and the cell-associated glycoprotein tissue factor (FVIIa/TF) initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. The critical role of the coagulation cascade in pathological thrombosis has been the basis for significant efforts to design selective inhibitors of the prot...

Selenium plays an important role in biological system due to its incorporation in glutathione peroxidases and thioredoxin reductase as prosthetic group, the pharmacological studies of synthetic organoseleno-compounds revealed these molecules to be used as antioxidants, enzyme inhibitors, neuroprotectors, antitumor, anti-infectious agents, cytokine inducers and immuno-modulators. The present stu...

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Factor Xa (FXa) emerged as a promising target for effective anticoagulation and several FXa inhibitors are now available for the prevention of venous thromboembolism. However, in previously reported pharmacokinetic/pharmacodynamic (PK/PD) models, the complex coagulation processes and detailed information of drug action are usually unclear, which makes it difficult to predict clinical outcome at...

Over the past forty years the availability of coagulation factor replacement therapy has greatly contributed to the improved care of people with hemophilia. Following the blood-borne viral infections in the late 1970s and early 1980, caused by coagulation factor concentrates manufactured using non-virally inactivated pooled plasma, the need for safer treatment became crucial to the hemophilia c...