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Biomap#23

Title: List of integrin inhibitors
 
Legend: Integrins are heterodimer transmembrane receptors for the extracellular matrix composed of an alpha and beta subunit. Natural integrin ligands include laminin, fibronectin, and vitronectin, but they also include fibrinogen and fibrin, thrombospondin, MMP-2, and FGF-2. Integrins bind ligands by recognizing short amino acid stretches on exposed loops, particularly the arginine-glycine-aspartic acid (RGD) sequence. On ligation, integrins mediate complex signaling events, alone or in combination with growth factor receptors, regulating cell adhesion, proliferation, survival, and migration by activating different pathways, such as integrin-linked kinase (ILK), protein kinase B (PKB/Akt), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NFkB). In resting vessels, integrins interact with the basal membrane, thereby maintaining vascular quiescence. During angiogenesis, they are essential for endothelial cell migration, proliferation, and survival. Of the 24 known integrin heterodimers, Vbeta3 and Vbeta5 were the first vascular integrins targeted to suppress tumor angiogenesis. In preclinical studies, pharmacologic inhibition of integrin function efficiently suppresses angiogenesis and inhibited tumor progression. Encouraging preclinical results prompted the development of integrin inhibitors (e.g. cilengitide, CNTO 95, Etaracizumab, Vitaxin, S-247) for clinical testing. REFERENCES: [1] Hehlgans S, Biochim Biophys Acta 2007, 1775:163-80. [2] Tucker GC, Curr Oncol Rep 2006, 8:96-103. [3] Cai W, Anticancer Agents Med Chem 2006, 6:407-28. [4] Dayam R, J Med Chem 2006, 49:4526-34. [5] Boswell CA, Mol Pharm 2008, 5:527-39.
Author: The MMMP Team (updated: December 2008)

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