Anti-Angiogenesis and Disintegrins

摘要: Angiogenesis is a critical process in tumor and disease progression. A number of features are central to both growth development, the recruitment invasion growing vascular network supplying with nutrients mechanism escape allow meastatic growth. One class molecules important blood vessel family cell surface receptors identified as integrins. Integrins α/β heterodimeric glycoproteins which different α subunits combine distinct β resulting range specificities toward various extracellular matrix (ECM) proteins. The RGD sequence found ECM proteins recognized by several classes integrins, allowing for linkage cytoskeletal associated integrins leads involvement bi-directional signaling that displays profound effects on cellular functions. Among these integrin mediated interactions adhesion endothelial cells cancer proteins, an interaction integral metastasis, angiogensis. Antibodies targeted have been shown retard subsequent induced angiogenesis. concern this approach antibody targets single integrin, may utilize other non-targeted circumvent type blockage. more broad spectrum agent available binds blocks function at time, agents disintegrin. Originally purified from venom Viperidae snakes, disintegrins role nature presumably block platelet aggregation following envenomation based activated It has observed overexpressed some types angiogenic vasculature similar affinity motifs Based disintegrin structure we developed recombinant form snake disintegrin, call vicrostatin (VCN). VCN potent anti-angiogenic/anti-tumor vitro vivo laboratory studies. Further development derived along new technology looking additional disintegrin-like offer novel therapeutic targeting