ART‐123: Recombinant Human Soluble Thrombomodulin

ABSTRACTART‐123 is a soluble form of recombinant human thrombomodulin comprising all extracellular domains of thrombomodulin. Bound to thrombin, ART‐123 inhibits its procoagulant activity and promotes activation of protein C. ART‐123 inhibits thrombin generation by the activation of protein C and the subsequent inactivation of factor Va in the presence of protein S. ART‐123 attenuates the extension of the clot by inhibiting further thrombin generation on clots, while other anticoagulants inhibit the initiation of clot formation. A higher concentration of ART‐123 is needed to affect clotting time and platelet aggregation than thrombin generation. Intravenous administration of ART‐123 is effective in animal models of disseminated intravascular coagulation (DIC), AV‐shunt, and other models with a wider safety margin than conventional anticoagulants. The plasma half‐life of ART‐123 is long, especially on subcutaneous injection. Clinical studies have been performed or are planned to evaluate the efficacy of ART‐123 in DIC and deep venous thrombosis (DVT). In clinical trials against DIC ART‐123 was well tolerated and showed a good dose‐response effect. These findings suggested that ART‐123 is a promising drug for thrombotic diseases.