Cilengitide

Cilengitide (EMD 121974) is a BBB-permeable integrins antagonist with IC₅₀s of 0.61 nM (α_νβ₃), 8.4 nM (α_νβ₅) and 14.9 nM (α₅β₁), respectively. Cilengitide inhibits the binding of α_νβ₃ and α_νβ₅ to Vitronectin with IC₅₀s of 4 nM and 79 nM, respectively. Cilengitide inhibits TGF-β/Smad signaling, mediates PD-L1 expression. Cilengitide also induces apoptosis, shows antiangiogenic effect in the research against glioblastoma and other cancers^[1][2][3]. IC50 & Target:IC50: 0.61 nM (α_vβ₃), 8.4 nM (α_vβ₅), 14.9 nM (α₅β₁)^[1]; 4 nM (α_vβ₃/Vitronectin), 79 nM (α_vβ₅/Vitronectin)^[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^[2].
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^[2].
Cilengitide inhibits the attachment of human umbilical vein endothelial cells to Vitronectin with an IC₅₀ of 2 μM^[2].
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^[3].
Cilengitide (5 μg/mL, 10 μg/mL; 2 weeks) inhibits colony formation of B16 and A375 cells^[3].
Cilengitide (0-20 μg/mL; 12 h) inhibits STAT3 phosphorylation to decrease the expression of PD-L1^[3].
In Vivo:Cilengitide (i.p. at 10, 50, and 250 μg three times per week) inhibits M21-L melanoma tumors growth in nude mice^[2].
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^[3].