Parmodulin 2

**Parmodulin 2** (ML161) is a small molecule allosteric modulator of protease-activated receptor 1 (PAR1), acting at the cytosolic face to bias signaling. It inhibits PAR1-mediated platelet aggregation (IC50 0.26 μM) induced by thrombin or PAR1 peptide agonists, blocks pro-thrombotic and pro-inflammatory endothelial responses like Weibel-Palade body exocytosis, NF-κB activation, and tissue factor expression, while stimulating cytoprotective pathways including Gβγ/PI3K/Akt signaling leading to stanniocalcin-1 upregulation. Developed through research on biased PAR1 ligands, it demonstrates antithrombotic and anti-inflammatory effects in preclinical models of thrombosis, inflammation, myocardial infarction, and sickle cell disease without prolonging coagulation times or blocking activated protein C (APC)-induced protection.[1][2][3][4][5]