Inhibitors of blood coagulation factor XIII

Abstract

The blood coagulation factor XIII (FXIII) plays an essential role in the stabilization of fibrin clots. This factor, belonging to the class of transglutaminases, catalyzes the final step of secondary hemostasis, i.e. the crosslinking of fibrin polymers. These crosslinks protect the clots against premature fibrinolysis. Consequently, FXIII is an interesting target for the therapeutic treatment of cardiovascular diseases. In this context, inhibitors can influence FXIII in the activation process of the enzyme itself or in its catalytic activity. To date, there is no FXIII inhibitor in medical application, but several studies have been conducted in the past. These studies provided a better understanding of FXIII and identified new lead structures for FXIII inhibitors. Next to small molecule inhibitors, the most promising candidates for the development of clinically applicable FXIII inhibitors are the peptide inhibitors tridegin and transglutaminase-inhibiting Michael acceptors (TIMAs) due to their selectivity towards activated FXIII (FXIIIa). In this review, select FXIII inhibitors and their pharmacological potential are discussed.

Keywords: Blood coagulation cascade; FXIIIa; FXIIIa inhibitor; Transglutaminase; Tridegin.