VE-1902-A direct thrombin inhibitor with reversible covalent mechanism of action shows efficacy with reduced bleeding in rodent models of thrombosis.
Anticoagulants
Direct thrombin inhibitor
Reduced bleeding
Thrombin
Thrombosis
Journal
Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
24
01
2020
revised:
18
03
2020
accepted:
15
04
2020
pubmed:
28
4
2020
medline:
22
6
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
High incidence of bleeding events remains a key risk for patients taking anticoagulants, especially those in need of long-term combination therapy with antiplatelet agents. As a consequence, patients may not receive clinically indicated combination antithrombotic therapy. Here, we report on VE-1902, a member of a novel class of precision oral anticoagulants (PROACs) that combines effective anticoagulation with reduced bleeding in preclinical testing. Acting through covalent, reversible active-site modification of thrombin similar to a previously described molecule [1], VE-1902 shows potency and selectivity for thrombin inhibition in human plasma comparable to clinically relevant direct thrombin inhibitors (DTI) such as argatroban and dabigatran (thrombin generation assay ETP EC By leaving platelet activation following vascular injury mostly unaffected, VE-1902, and the PROACs more generally, represent a new generation of precision anticoagulants with reduced bleeding risk.
Identifiants
pubmed: 32339947
pii: S0049-3848(20)30136-5
doi: 10.1016/j.thromres.2020.04.020
pmc: PMC7936662
mid: NIHMS1675657
pii:
doi:
Substances chimiques
Anticoagulants
0
Antithrombins
0
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112-121Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL049413
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139554
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147821
Pays : United States
Organisme : NHLBI NIH HHS
ID : R29 HL049413
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest E.D.C. has a financial interest in Verseon Corporation.
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