Cilengitide (EMD 121974) is an antagonist for αvβ3 and αvβ5 integrin receptors. It effectively blocks the adhesion of human melanoma M21 and UCLA-P3 human lung carcinoma cell lines to vitronectin, demonstrating inhibitory concentrations (IC50s) of 0.4 μM for both[1]. Exposure to Cilengitide at concentrations above 1 µM induces cytotoxic effects that are both concentration- and time-dependent[2]. Exposure to Cilengitide at concentrations above 1 µM induces cytotoxic effects that are both concentration- and time-dependent[2].
体内研究
In nude mice implanted with M21-L melanoma tumors, intraperitoneal (i.p.) doses of Cilengitide at 10, 50, and 250 μg, administered thrice weekly, led to significant tumor growth inhibition, evident in the reduction of tumor volume by 55%, 75%, and 89%, and tumor weight by 23%, 38%, and 61%, respectively, compared to controls[2].
In rats, the systemic pharmacokinetics of Cilengitide, administered i.p., remained consistent regardless of isolation limb perfusion (ILP) with Cilengitide alone or combined with Melphalan, TNF, or both. Systemic levels of Cilengitide reached approximately 20 µg/mL (about 35 µM) within 10 minutes post-administration and increased to about 40 µg/mL (roughly 70 µM) within the first hour. Subsequently, serum levels of Cilengitide decreased, with an elimination half-life of 2.1 hours[3].
体外研究
Cilengitide (EMD 121974) is an antagonist for αvβ3 and αvβ5 integrin receptors. It effectively blocks the adhesion of human melanoma M21 and UCLA-P3 human lung carcinoma cell lines to vitronectin, demonstrating inhibitory concentrations (IC50s) of 0.4 μM for both[1]. Exposure to Cilengitide at concentrations above 1 µM induces cytotoxic effects that are both concentration- and time-dependent[2].
Exposure to Cilengitide at concentrations above 1 µM induces cytotoxic effects that are both concentration- and time-dependent[2].
Cilengitide TFA/西仑吉肽 三氟醋酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HUVECs
2 nM
24 h
To evaluate the promoting effect of Cilengitide on HUVEC migration. The results showed that MC-T-DOX significantly increased the migration area of HUVECs, indicating that it promoted endothelial cell migration by releasing Cilengitide through MT1-MMP activation.
Adv Sci (Weinh). 2020 Jul 10;7(17):1902746.
HUVECs
2 nM
8 h
To evaluate the effect of Cilengitide on HUVEC tube formation. The results showed that MC-T-DOX significantly increased the number and length of tube-like structures, indicating that it promoted angiogenesis by releasing Cilengitide through MT1-MMP activation.
Adv Sci (Weinh). 2020 Jul 10;7(17):1902746.
U87ΔEGFR cells
1.0 μM
16 h
To study the effect of Cilengitide on gene expression in U87ΔEGFR cells, results showed changes in gene expression after Cilengitide treatment.
Transl Oncol. 2014 Apr;7(2):292-302.e1.
MRC-5 cells
0.5 μM
To investigate the inhibitory effect of Cilengitide on TGF-β1 activation in MRC-5 cells, results showed that Cilengitide inhibited TGF-β1 activation and its downstream signaling pathway.
Clin Transl Med. 2024 Jan;14(1):e1546.
HSC3 cells
10 μM
15 min
Inhibit the interaction between β5-integrin and the extracellular matrix, preventing FCL formation
Nat Commun. 2022 Feb 16;13(1):905.
A2780 ovarian cancer cells
1 μM
20 min
Promoted α5β1 integrin recycling, increased coprecipitation of RCP with α5β1, and drove tumor cell migration into three-dimensional matrices
J Cell Biol. 2008 Oct 6;183(1):143-55.
Cilengitide TFA/西仑吉肽 三氟醋酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Hypoperfused pancreatic cancer mouse model
Intravenous injection
8.5 nM/kg
Every 4 days for three cycles
To evaluate the anti-angiogenic and anti-tumor effects of MC-T-DOX in a pancreatic cancer mouse model. The results showed that MC-T-DOX significantly increased tumor vascular density and the percentage of functional vessels, and improved tumor blood perfusion, resulting in significant tumor growth inhibition.
Adv Sci (Weinh). 2020 Jul 10;7(17):1902746.
Nude mice and rats
U87ΔEGFR brain tumor model
Intraperitoneal injection
10 mg/kg
Three times per week for 13 days
To study the effect of Cilengitide in combination with Bevacizumab on glioma invasiveness, results showed that combination therapy significantly reduced the depth of tumor invasion.
Transl Oncol. 2014 Apr;7(2):292-302.e1.
BALB/c nude mice
Patient-derived xenograft (PDX) models
Intratumor injection
10 mg/kg
Once a week, 4 weeks
Combination treatment with EMD and bevacizumab significantly inhibited tumor growth and decreased the number of VM channels and microvessels
Mol Oncol. 2021 Dec;15(12):3447-3467.
Mice
Radiation-induced pulmonary fibrosis model
Intraperitoneal injection
15 or 75 mg/kg
Once daily for 8 weeks
To investigate the protective effect of Cilengitide on radiation-induced pulmonary fibrosis, results showed that Cilengitide significantly attenuated lung fibrosis and improved survival in mice.
Clin Transl Med. 2024 Jan;14(1):e1546.
BALB/c nude mice
HepG2 tumor model
Intravenous injection
100 μg
Single dose, lasting 30 minutes
Used to block integrin αvβ3 receptors and validate the targeting of nanodots. Results showed significantly reduced tumor fluorescence signal in the blocking group, indicating that Cilengitide effectively inhibited the targeted accumulation of nanodots.
Theranostics. 2019 Feb 12;9(5):1264-1279
Mice
Liver fibrosis model
Intraperitoneal injection
30 mg/kg
Once daily for 3 weeks
Cilengitide treatment significantly reduced liver fibrosis indicators in Ecm1Δhep mice, including serum ALT and AST activities, inflammatory damage, and collagen deposition.
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