<i>In Silico</i> and <i>In Vitro</i> Studies of Potential Novel Vitamin K Epoxide Reductase (VKOR) Inhibitors Suggest an Updated Structure-Activity Relationship.

ABSTRACT: Vitamin K epoxide reductase (VKOR) is an enzyme involved in the activation of several clotting factors, making its inhibition a well-known mechanism of anticoagulant action. Though the VKOR inhibitor warfarin remains essential and popular today, its adverse effects still make it a high-risk drug. This study intends to identify novel compounds with predicted VKOR inhibition and pharmacokinetic stability and explain the mechanistic basis of their action. A combination of pharmacophore modeling, druglikeness prediction, and molecular docking was used to find hits from existing compound libraries. The top hits showed in vitro activity at the micromolar level in a cell-based VKOR inhibition assay using human embryonic kidney 293 cells, led by A114 (IC₅₀ = 5.51 μM) and A116 (IC

SUBMITTER: Mortel SLR 

PROVIDER: S-EPMC12224098 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature