JSM 6427

Wet AMD causes vision loss due to abnormal growth of new blood vessels in the choriocapillaris. New blood vessels arise as a result of proliferation, migration and differentiation of pre-existing blood vessel cells (endothelium). In order for the endothelium to form functional new blood vessels, they make use of cell surface adhesion receptors called integrins. These molecules are critical for the interaction between a vascular endothelial cell and its surrounding environment. The disruption of the integrin receptor represents a new therapeutic approach for the treatment of AMD by addressing different modes of action. JSM-6427 acts as an antagonist of the integrin α5β1 receptor. Integrin α5β1 is the prototype integrin and a therapeutic target in a final common pathway downstream of various blood vessel formation inducing factors including VEGF and bFGF (basic Fibroblast Growth Factor). JSM-6427 exhibits a 1700-fold selectivity for the α5β1 integrin and prevents α5β1 from binding to fibronectin, a glycoprotein that is an important component of the extracellular matrix that helps to maintain cell structure and function by acting (among others) as a binding site for cell surface receptors.