Integrin alpha-V beta-3 (αvβ3)

Integrin alpha-V beta-3 is a heterodimeric transmembrane glycoprotein composed of the alpha-V (CD51) and beta-3 (CD61) subunits [1]. It functions as a receptor for extracellular matrix proteins containing the RGD (Arg-Gly-Asp) motif, such as vitronectin and fibronectin, playing a pivotal role in cell adhesion, migration, and survival [2]. This integrin is highly expressed on the surface of activated endothelial cells during angiogenesis and on various tumor cells, where it promotes metastasis and tumor progression [3]. In addition to oncology, it is critical in bone resorption by mediating osteoclast attachment to the bone matrix [4]. Therapeutic approaches have focused on RGD-mimetic peptides and monoclonal antibodies, such as cilengitide and etaracizumab, to inhibit its activity [5]. Despite its clear role in disease, clinical trials have faced challenges, including potential paradoxical activation and limited efficacy as a monotherapy [6].

Other names

Vitronectin receptorCD51/CD61ITGAV/ITGB3Integrin alphaVbeta3Integrin alpha-V/beta-3

Competitive inhibition of the RGD-binding site on the integrin heterodimer, preventing interaction with extracellular matrix proteins like vitronectin and fibronectin [5]. This blockade inhibits intracellular signaling through focal adhesion kinase (FAK) and Src kinase, which are essential for cell migration, proliferation, and survival [2].