Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa.
BAY 2433334
anticoagulant
asundexian
factor XIa inhibitor
thrombosis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
02
03
2022
received:
19
11
2021
accepted:
07
03
2022
pubmed:
16
3
2022
medline:
25
5
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Activated coagulation factor XI (FXIa) contributes to the development and propagation of thrombosis but plays only a minor role in hemostasis; therefore, it is an attractive antithrombotic target. To evaluate the pharmacology of asundexian (BAY 2433334), a small molecule inhibitor targeting FXIa, in vitro and in various rabbit models. The effects of asundexian on FXIa activity, selectivity versus other proteases, plasma thrombin generation, and clotting assays were evaluated. Antithrombotic effects were determined in FeCl Asundexian inhibited human FXIa with high potency and selectivity. It reduced FXIa activity, thrombin generation triggered by contact activation or low concentrations of tissue factor, and prolonged activated partial thromboplastin time in human, rabbit, and various other species, but not in rodents. In the FeCl Asundexian is a potent oral FXIa inhibitor with antithrombotic efficacy in arterial and venous thrombosis models in prevention and intervention settings, without increasing bleeding.
Sections du résumé
BACKGROUND
Activated coagulation factor XI (FXIa) contributes to the development and propagation of thrombosis but plays only a minor role in hemostasis; therefore, it is an attractive antithrombotic target.
OBJECTIVES
To evaluate the pharmacology of asundexian (BAY 2433334), a small molecule inhibitor targeting FXIa, in vitro and in various rabbit models.
METHODS
The effects of asundexian on FXIa activity, selectivity versus other proteases, plasma thrombin generation, and clotting assays were evaluated. Antithrombotic effects were determined in FeCl
RESULTS
Asundexian inhibited human FXIa with high potency and selectivity. It reduced FXIa activity, thrombin generation triggered by contact activation or low concentrations of tissue factor, and prolonged activated partial thromboplastin time in human, rabbit, and various other species, but not in rodents. In the FeCl
CONCLUSIONS
Asundexian is a potent oral FXIa inhibitor with antithrombotic efficacy in arterial and venous thrombosis models in prevention and intervention settings, without increasing bleeding.
Identifiants
pubmed: 35289054
doi: 10.1111/jth.15700
pmc: PMC9313898
pii: S1538-7836(22)00195-7
doi:
Substances chimiques
Anticoagulants
0
Fibrinolytic Agents
0
Platelet Aggregation Inhibitors
0
Factor XIa
EC 3.4.21.27
Thrombin
EC 3.4.21.5
Ticagrelor
GLH0314RVC
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1400-1411Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2022 Bayer AG. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
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