MNK1-MYH9 stabilizer MD2 is a molecular stabilizer of the interaction between MNK1 and MYH9, specifically occupies the ATP-binding pocket within the kinase domain of MNK1, binds directly to MNK1 with SPR KD of 9.8 uM, exhibits potent antithrombotic effect.
MD2 significantly preserves the interaction between MNK1 and MYH9.
specifically occupies the ATP-binding pocket within the kinase domain of MNK1, binds directly to MNK1 with SPR KD of 9.8 uM.
MD2 demonstrates potent anti-platelet activity, significantly inhibits thrombin-induced aggregation in LTA assays.
MD2 effectively suppressed the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), a classic downstream target of MNK1.
MD2 inhibited over 90% of MNK1 and MNK2 activities, while exhibiting minimal inhibitory effects against other platelet-relevant kinases such as Src and Syk.
MD2 acts as a molecular stabilizer, locking the MNK1-MYH9 complex in a quiescent conformation to prevent the cytoskeletal engagement of YAP1 during platelet activation.
MD2 specifically targets the intracellular MNK1-MYH9-YAP1 axis, potently suppressing platelet activation while sparing global hemostatic function.
MD2 effectively suppresses platelet-mediated neutrophil activation, thereby preventing the propagation of NET-dependent thrombosis.
MD2 (1.25 or 2.5 mg/kg) exhibits potent antithrombotic efficacy in murine models representing arterial and venous pathologies, does not significantly affect hemostasis.