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Purity: ≥98%
Cilengitide (also known as EMD 121974, NSC 707544) is a highly potent integrin inhibitor for the αvβ3 receptor and the αvβ5 receptor with IC50 of 4.1 nM and 79 nM in cell-free assays, respectively; it showed ~10-fold selectivity against gpIIbIIIa. Cilengitide is a cyclic Arg-Gly-Asp based peptide with potential antineoplastic activity and has been extensively studied for its anticancer application. The mechanism of action for cilengitide is to bind to and inhibit the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. Cilengitide is currently undergoing phase 2 clinical trials, and the European Medicines Agency has granted cilengitide orphan drug status.
| ln Vitro |
Cilengitide is a pentapeptide with cyclized RGD (Arg-Gly-Asp) motif. Cilengitide inhibits the attachment and migration of endothelial cells mediated by integrins αvβ3 and ανβ5[2]. Cilengitide, in cell adhesion studies evaluating the human melanoma M21 or UCLA-P3 human lung carcinoma cell lines, inhibits integrin-mediated binding to Vitronectin with IC50s of 0.4 and 0.4 μM[2]. With an IC50 of 2 μM, celenegitide prevents human umbilical vein endothelial cells from adhering to vitronectin[2]. Cilengitide (5 μg/mL; 12 h) induces apoptosis in B16 and A375 cells and inhibits the viability of melanoma cells in vitro (0–1 mg/mL; 24-72 h)[3]. B16 and A375 cells' ability to form colonies is inhibited by celenigitide (5 μg/mL, 10 μg/mL; 2 weeks)[3]. PD-L1 expression is reduced by inhibiting STAT3 phosphorylation with celenigitide (0–20 μg/mL; 12 h)[3].
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| ln Vivo |
In nude mice, cilengitide (ip at 10, 50, and 250 μg three times per week) inhibits the growth of M21-L melanoma tumors[2]. In the B16 murine melanoma model, cleengitide (50 mg/kg; intraperitoneal; daily) improves CD8+ T cell function and supports anti-PD1 efficacy with anti-PD1 monoclonal antibody[3].
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| Cell Assay |
Western Blot Analysis[3]
Cell Types: B16 and A375 cells Tested Concentrations: 0, 5, 10, and 20 μg/mL Incubation Duration: 12 hrs (hours) Experimental Results: Suppressed PD-L1 expression and STAT3 phosphorylation at concentrations greater than 5 μg/mL. Apoptosis Analysis[3] Cell Types: B16 and A375 cells Tested Concentrations: 5 μg/mL Incubation Duration: 12 hrs (hours) Experimental Results: Resulted apoptosis rates in B16 and A375 cells of 15.27% and 14.89%, respectively. |
| Animal Protocol |
Animal/Disease Models: Nude mice bearing M21-L melanoma tumors[2]
Doses: 10, 50, and 250 μg Route of Administration: Dosed ip three times per week Experimental Results: 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/Disease Models: Female C57BL/6 mice (6-8 weeks old) with B16 cells sc[3] Doses: 50 mg/kg; with or without 10 mg/kg Anti-PD1 monoclonal antibody or isotype control ip every 3 days; Route of Administration: intraperitoneal (ip)injection; daily Experimental Results: Downregulated the expression of PD-L1 via STAT3 pathway and diminished the expression of PD-L1. |
| References |
[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.
[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. [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. |
| Molecular Formula |
C₂₇H₄₀N₈O₇
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| Molecular Weight |
588.66
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| CAS # |
188968-51-6
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| Related CAS # |
Cilengitide TFA;199807-35-7
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| SMILES |
O=C(NCC(N[ C@H](C(N[ C@H](CC1=CC=CC=C1)C(N([ C@H]2C(C)C)C)=O)=O)CC(O)=O)=O)[ C@H](CCCNC(N)=N)NC2=O
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (169.88 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6988 mL | 8.4939 mL | 16.9877 mL | |
| 5 mM | 0.3398 mL | 1.6988 mL | 3.3975 mL | |
| 10 mM | 0.1699 mL | 0.8494 mL | 1.6988 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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