{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jankowski W"],"funding":["U.S. Department of Health & Human Services | U.S. Food and Drug Administration","U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)"],"pagination":["3912"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11082157"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC bindin"],"journal":["Nature communications"],"pubmed_title":["Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding."],"pmcid":["PMC11082157"],"funding_grant_id":["None"],"pubmed_authors":["Ovanesov MV","Freedberg D","Rawal A","Jankowski W","Surov SS","Hernandez NE","Battistel M","Sauna ZE"],"additional_accession":[]},"is_claimable":false,"name":"Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.","description":"Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC bindin","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-03T05:00:15.335Z","creation":"2026-05-28T03:06:44.503Z"},"accession":"S-EPMC11082157","cross_references":{"pubmed":["38724509"],"doi":["10.1038/s41467-024-48278-1"]}}