Cilengitide

Cilengitide is a potent integrin inhibitor for αvβ3 receptor and αvβ5 receptor with IC50 of 4.1 nM and 79 nM in cell-free assays, respectively; ~10-fold selectivity against gpIIbIIIa. Phase 2. (In Vitro) :Cilengitide is a cyclized RGD (Arg-Gly-Asp motif) -containing pentapeptide. Cilengitide blocks integrin ανβ3- and ανβ5-mediated endothelial cell attachment and migration.Cilengitide inhibits integrin-mediated binding to Vitronectin with IC50s of 0.4 and 0.4 μM in cell adhesion studies assessing the human melanoma M21 or UCLA-P3 human lung carcinoma cell lines.Cilengitide inhibits the attachment of human umbilical vein endothelial cells to Vitronectin with an IC50 of 2 μM.Cilengitide (0-1 mg/mL; 24-72 h) inhibits cell viability of melanoma cells in vitro and (5 μg/mL; 12 h) induces B16 and A375 cells apoptosis.Cilengitide (5 μg/mL, 10 μg/mL; 2 weeks) inhibits colony formation of B16 and A375 cells. (In Vivo) :Cilengitide (i.p. at 10, 50, and 250 μg three times per week) inhibits M21-L melanoma tumors growth in nude mice.Cilengitide (50 mg/kg; i.p.; daily) enhances the function of CD8+ T cells and promotes anti-PD1 efficacy with Anti-PD1 monoclonal antibody in B16 murine melanoma model.