Cilengitide

• CAT Number: I002437
• CAS Number: 188968-51-6
• Molecular Formula: C27H40N8O7
• Molecular Weight: 588.66
• Purity: ≥95%
• Synonyms: 2-[(2S,5R,8S,11S)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-7-methyl-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
• InChI: InChI=1S/C27H40N8O7/c1-15(2)22-25(41)33-17(10-7-11-30-27(28)29)23(39)31-14-20(36)32-18(13-21(37)38)24(40)34-19(26(42)35(22)3)12-16-8-5-4-6-9-16/h4-6,8-9,15,17-19,22H,7,10-14H2,1-3H3,(H,31,39)(H,32,36)(H,33,41)(H,34,40)(H,37,38)(H4,28,29,30)/t17-,18-,19+,22-/m0/s1
• InChIKey: AMLYAMJWYAIXIA-VWNVYAMZSA-N
• SMILES: CC(C)C1C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)N1C)CC2=CC=CC=C2)CC(=O)O)CCCN=C(N)N

Cilengitide (EMD 121974) is a potent integrins antagonist with IC50s of 0.61 nM (ανβ3), 8.4 nM (ανβ5) and 14.9 nM (α5β1), respectively. Cilengitide inhibits the binding of ανβ3 and ανβ5 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].
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].
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].

Reference

[1]. Kapp TG, et al. A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins. Sci Rep. 2017 Jan 11;7:39805.
 [Content Brief]

[2]. Hariharan S, et al. Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrinreceptor antagonist, Cilengitide (EMD 121974), in patients with advanced solid tumors. Ann Oncol. 2007 Aug;18(8):1400-7.
 [Content Brief]

[3]. Pan X, et al. Cilengitide, an αvβ3-integrin inhibitor, enhances the efficacy of anti-programmed cell death-1 therapy in a murine melanoma model. Bioengineered. 2022 Feb;13(2):4557-4572.
 [Content Brief]