Cyclo(RGDyK)

Target: αVβ3 integrin

IC50: 20 nM

Cyclo(RGDyK) is a selective and potent αVβ3 integrin inhibitor with IC50 value of 20 nM [1]. The αVβ3 integrin, expressed on various malignant human tumors and on endothelial cells, plays an important role in tumor-induced angiogenesis and tumor metastasis. Therefore, αVβ3 integrin is a potential therapeutic target for tumor disease. Inhibition of αVβ3 integrin by αVβ3 antagonists not only blocked blood vessel formation but further led to tumor regression [1].

In vitro: Cyclo(RGDyK) conjugation facilitated intracellular drug delivery of polymeric micelles to neovasculature (HUVECs) and tumor cells in which integrin is overexpressed [2]. In addition, Cyclo(RGDyK) showed high affinity and selectivity for αVβ3 integrin over αVβ5 and αIIbβ3 [1].

In vivo: Cyclo(RGDyK) (1 nM, i.v. injection) blocked the increase of αVβ3 integrin expression in the intima of the left stenotic carotid artery of apoE-/- mice [2].

References:
1.  Haubner R, Wester HJ, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001;42(2):326-36.
2.  Yin J, Li Z, Yang T, Wang J, Zhang X, Zhang Q. Cyclic RGDyK conjugation facilitates intracellular drug delivery of polymeric micelles to integrin-overexpressing tumor cells and neovasculature. J Drug Target. 2011;19(1):25-36.