Screening of a Library for Factor VIIa Inhibitors

Background: As an alternative to the anticoagulant’s strategy using direct or indirect anti-Xa drugs, considering other targets upstream in the coagulation cascade such as anti-Factor VIIa could represent an effective and safer strategy in coagulation and pathological angiogenesis. Objective: The objective of the study was to assess a high technology methodology composed of virtual screening, anticoagulant, and anti-angiogenesis assays to identify potent small-molecule FVIIa inhibitors. Methods: Chemical databanks were screened to select molecules bearing functional groups that could fit into the active site of FVIIa, which were then tested. Ligands assigned with the lowest scores were retained and then biologically assessed. Results: From the 500 molecules considered, 8 chemical structures revealed to be effective compounds in vitro and to inhibit angiogenesis in the chick chorioallantoic membrane (CAM) model. Conclusion: New potent small-molecule FVIIa inhibitors have been identified; further biochemical and chemical developments would be investigated directly from the selected scaffolds.