Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threa...Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threatening disseminated intravascular coagulation ( DIC),and deep venous thromboembolism (DVT) and pulmonary embolism.Antithrombosis encompasses several aspects:coagulation,platelets,fibrinolysis,vascular endothelial cells,hemodynamics and hemorheology.Among them,anticoagulation is a fundamental step in antithrombotic therapy.Existing anticoagulants inhibit coagulation factors effectively,and are countered by substantial limitations with severe bleeding risk.For newer generation anticoagulant development,it is important to achieve a low ratio of hemorrhagic risk/antithrombotic benefit.展开更多
Coagulation Factor Xa(FXa)is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways.The inhibition of FXa is an effective approach against thrombotic diseases.In the present stu...Coagulation Factor Xa(FXa)is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways.The inhibition of FXa is an effective approach against thrombotic diseases.In the present study,a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based(pharmacophore)virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules).The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa,and 10 novel structural compounds were discovered as potent candidate molecules.This work could be helpful in further design and development of FXa inhibitors.展开更多
文摘Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threatening disseminated intravascular coagulation ( DIC),and deep venous thromboembolism (DVT) and pulmonary embolism.Antithrombosis encompasses several aspects:coagulation,platelets,fibrinolysis,vascular endothelial cells,hemodynamics and hemorheology.Among them,anticoagulation is a fundamental step in antithrombotic therapy.Existing anticoagulants inhibit coagulation factors effectively,and are countered by substantial limitations with severe bleeding risk.For newer generation anticoagulant development,it is important to achieve a low ratio of hemorrhagic risk/antithrombotic benefit.
基金the Science and Technology Innovation Talent Project of Sichuanprovince (Grant number 2016073).
文摘Coagulation Factor Xa(FXa)is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways.The inhibition of FXa is an effective approach against thrombotic diseases.In the present study,a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based(pharmacophore)virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules).The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa,and 10 novel structural compounds were discovered as potent candidate molecules.This work could be helpful in further design and development of FXa inhibitors.
