Inhibitors of cellular adhesion molecules

Another approach to antiangiogenic therapy is to inhibit the adhesive interactions required by angiogenesis vascular endothelial cells. The migration of endothelial cells is dependent on their adhesion to extracellular matrix proteins through a variety of cell adhesion receptors known as integrins, especially integrin avp3.33 Integrin binds to an arginine-glycine-aspartic acid (RGD) sequence, which can be found in several extracellular matrix proteins. The antiangiogenic cyclic peptide cydo-(Arg-Gly-Asp-d-Phe-d-NMeVal) (cilengitide, 10.9) inhibits avp3 and is undergoing clinical trials for brain and solid tumors.

avp5 is another RGD-dependent adhesion receptor that plays a critical role in angiogenesis, and hence selective dual avp3/avp5 antagonists, such as SCH-221153, have been proposed as a novel class of angiogenesis and tumor-growth inhibitors.34

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