Cilengitide

SKU: orb1225823

Description

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.

Key Properties

• CAS Number: 188968-51-6
• MW: 588.66
• Purity: >98% (HPLC)
• Formula: C₂₇H₄₀N₈O₇
• SMILES: CC(C)[C@H]1C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C(=O)N1C)CC2=CC=CC=C2)CC(=O)O)CCCN=C(N)N
• Target: Integrin
• Solubility: Water: 8 mg/mL (13.59 mM); DMSO: 100 mg/mL (169.87 mM)

Bioactivity

• 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. Animal model: Nude mice bearing M21-L melanoma tumors. Dosage: 10, 50, and 250 μg. Administration: Dosed i.p. three times per week. Result: Demonstrated inhibition of tumor growth with a reduction in both tumor volume (55%, 75%, and 89%, respectively) and tumor weight (23%, 38%, and 61%, respectively), when compared to controls. Animal model: Female C57BL/6 mice (6-8 weeks old) with B16 cells s. c. Dosage: 50 mg/kg; with or without 10 mg/kg Anti-PD1 monoclonal antibody or isotype control i.p. every 3 days. Administration: Intraperitoneal injection; daily. Result: Downregulated the expression of PD-L1 via STAT3 pathway and decreased the expression of PD-L1.
• 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. Cilengitide (0-20 μg/mL; 12 h) inhibits STAT3 phosphorylation to decrease the expression of PD-L1. Western blot analysis. Cell line: B16 and A375 cells. Concentration: 0, 5, 10, and 20 μg/mL. Incubation time: 12 hours. Result: Suppressed PD-L1 expression and STAT3 phosphorylation at concentrations greater than 5 μg/mL. Apoptosis Analysis Cell line: B16 and A375 cells. Concentration: 5 μg/mL. Incubation time: 12 hours. Result: Resulted apoptosis rates in B16 and A375 cells of 15.27% and 14.89%, respectively.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EMD 121974

Quick Database Links

Gene Symbol

Integrin