MN-447 and MN-462 represent new approaches to blood clot formation and lysis.
MediciNova acquired two small molecule cardiovascular agents from Meiji Seika Kaisha for global markets with the exception of Japan and other selected Asian countries. MN-447 and MN-462 are antithrombic agents that show new approaches to blood clot formation and lysis, respectively. MediciNova expects that they will treat a variety of thrombotic disorders.
“MN-447 and MN-462 represent potentially important new interventions to treat thrombosis-related cardiovascular diseases (CVD) and commercially valuable additions to MediciNova’s advancing portfolio of product candidates,” says Yuichi Iwaki, M.D., Ph.D., executive chairman and CEO of MediciNova.
MN-447 is a cardioprotective, antiplatelet agent that acts as a potent dual antagonist of glycoprotein (GP) IIbIIIa and integrin alpha-v-beta-3 receptors that play key roles in blood clot formation and various cell behaviors and functions, such as leukocyte adhesion. It acts downstream by inhibiting the cross linking of platelets via fibrinogen bridges to GP IIbIIIa receptors. Inhibition of integrin alpha-v-beta-3 receptors has been linked to an inhibition of leukocyte adhesion to endothelium, reduction of hyperplasia, and lumen stenosis in response to vascular injury.
The dual inhibitory activity of MN-447 produced superior cardioprotective efficacy, such as reduction in infarct size after reperfusion compared to inhibition of the GP IIbIIIa receptor alone, and showed a low risk of bleeding in animal models of myocardial infarction and unstable angina.
MN-462 is a selective inhibitor of a key enzyme in the intrinsic antifibrinolytic mechanism, plasma carboxypeptidase B (CPB), which inhibits physiological fibrinolysis. By enhancing intrinsic fibrinolysis through plasma CPB inhibition, MN-462 has the potential to both reduce and prevent thrombus or blood clot formation as well as to dissolve formed thrombus.
MN-462 has demonstrated significant fibrinolytic-enhancing and antithrombotic activities as monotherapy in several thrombosis models as well as activities when used as an adjunct to fibrinolytics, such as tissue plasminogen activator (t-PA) in preclinical studies. The effect of MN-462 in enhancing the intrinsic fibrinolytic process has also been observed to result in a low risk of bleeding.
Given the high mortality and morbidity rates associated with CVD, MediciNova believes there is an urgent need for more targeted therapies that can intervene in known molecular pathways and minimize damage to the heart and related tissues.
