Evaluation of Serine Protease Inhibitors as Potent FVIIa-sTF Inhibitors in the Blood Coagulation Cascade

Serine proteases are involved in the blood coagulation cascade-composed of intrinsic, extrinsic, and common pathways affecting coagulation responses. Among the three pathways of the blood coagulation cascade involving serine proteases, this review focuses on serine protease inhibitors of the understudied extrinsic pathway, which is responsible for bleeding and bleeding complications targeting the (activated factor VII-Tissue Factor) fVIIa-TF complex. In lieu of our search for fVIIa-soluble TF (fVIIa-sTF) inhibitors or scaffolds, we review the serine protease inhibitors present as synthetic and natural products, which are involved in the blood coagulation cascade, and compare them with the serine protease peptide inhibitors found in toxic Microcystis cyanobacteria. Some scaffolds for the extrinsic pathway as inhibitors from the toxic Microcystis cyanobacteria will be identified in the review.