Cilengitide
(Synonyms: 西仑吉肽; EMD 121974) 目录号 : GC13559
Cilengitide是一种环化五肽，是一种强效整合素拮抗剂，对ανβ3、ανβ5和α5β1的IC50值分别为0.61nM、8.4nM和14.9nM。
Cas No.:188968-51-6
Sample solution is provided at 25 µL, 10mM.
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Cilengitide, a cyclized pentapeptide, is a potent integrins antagonist with IC50 values of 0.61nM, 8.4nM and 14.9nM for ανβ3, ανβ5, and α5β1, respectively[1]. Cilengitide inhibits binding of isolated ανβ3 and ανβ5 to vitronectin with an IC50 value of 4 and 79nM, respectively[2]. Cilengitide targets integrin dimers ITGAV:ITGB3 and ITGAV:ITGB5, and induces death in breast cancer cells with low integrin abundance[3]. Cilengitide has been widely used in various cancer cell models to block integrin-mediated cell adhesion and migration[4].
In vitro, Cilengitide treatment for 24 hours significantly inhibited the viability of A375 cells, with an IC50 value of 5µg/ml[5]. Treatment with 50μg/ml Cilengitide for 72 hours significantly inhibited the adhesion of HMEC-1 endothelial cells on the culture dish and induced cell apoptosis[6]. Treatment with 100μg/ml Cilengitide for 3 days significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells[7].
In vivo, Cilengitide treatment via daily intraperitoneal injection at a dose of 75mg/kg/day for 10 days, combined with two brain X-ray irradiations (5Gy; on the third and sixth days after tumor establishment), significantly inhibited the growth of brain tumors in mice and reduced tongue-like brain invasion[8]. Forty-eight hours after a single intraperitoneal injection of 4mg/kg of Cilengitide into a rat model of glioma xenografts, significant autophagy was induced in the xenograft tumors[9].
References:
[1] Kapp T G, Rechenmacher F, Neubauer S, et al. A comprehensive evaluation of the activity and selectivity profile of ligands for RGD-binding integrins[J]. Scientific reports, 2017, 7(1): 39805.
[2] Hariharan S, Gustafson D, Holden S, et al. Assessment of the biological and pharmacological effects of the ανβ3 and ανβ5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors[J]. Annals of oncology, 2007, 18(8): 1400-1407.
[3] Girnius N, Henstridge A Z, Marks B, et al. Cilengitide sensitivity is predicted by overall integrin expression in breast cancer[J]. Breast Cancer Research, 2024, 26(1): 187.
[4] Reardon D A, Nabors L B, Stupp R, et al. Cilengitide: an integrin-targeting arginine–glycine–aspartic acid peptide with promising activity for glioblastoma multiforme[J]. Expert opinion on investigational drugs, 2008, 17(8): 1225-1235.
[5] Pan X, Yi M, Liu C, et al. Cilengitide, an αvβ3-integrin inhibitor, enhances the efficacy of anti-programmed cell death-1 therapy in a murine melanoma model[J]. Bioengineered, 2022, 13(2): 4557-4572.
[6] Oliveira-Ferrer L, Hauschild J, Fiedler W, et al. Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway[J]. Journal of Experimental & Clinical Cancer Research, 2008, 27(1): 86.
[7] Bretschi M, Merz M, Komljenovic D, et al. Cilengitide inhibits metastatic bone colonization in a nude rat model[J]. Oncology reports, 2011, 26(4): 843-851.
[8] Wilisch-Neumann A, Kliese N, Pachow D, et al. The integrin inhibitor cilengitide affects meningioma cell motility and invasion[J]. Clinical Cancer Research, 2013, 19(19): 5402-5412.
[9] Lomonaco S L, Finniss S, Xiang C, et al. Cilengitide induces autophagy-mediated cell death in glioma cells[J]. Neuro-oncology, 2011, 13(8): 857-865.
Cilengitide是一种环化五肽，是一种强效整合素拮抗剂，对ανβ3、ανβ5和α5β1的IC50值分别为0.61nM、8.4nM和14.9nM[1]。Cilengitide抑制分离的ανβ3和ανβ5与vitronectin的结合，IC50值分别为4nM和79nM[2]。Cilengitide靶向整合素二聚体ITGAV:ITGB3和ITGAV:ITGB5，并诱导整合素丰度低的乳腺癌细胞死亡[3]。Cilengitide已广泛用于各种癌细胞模型，以阻断整合素介导的细胞粘附和迁移[4]。
在体外，Cilengitide处理24小时以IC50值为5µg/ml显著抑制了A375细胞的活力[5]。用50μg/ml的Cilengitide处理72小时显著抑制了HMEC-1内皮细胞在培养皿上的粘附并诱导了细胞凋亡[6]。用100μg/ml的Cilengitide处理3天显著抑制了MDA-MB-231细胞的增殖、迁移和侵袭[7]。
在体内，每日腹腔注射75mg/kg/day剂量的Cilengitide连续10天，并结合两次脑部X射线照射（5Gy；于成瘤后第三天和第六天），显著抑制了小鼠脑肿瘤的生长并减少了舌状脑侵袭[8]。在胶质瘤异种移植大鼠模型中单次腹腔注射4mg/kg剂量的Cilengitide 48小时后，显著诱导了异种移植肿瘤中的自噬[9]。
| Cell experiment [1]: | |
Cell lines | A375 cells |
Preparation Method | A375 cells were cultured in Dulbecco Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS) at 37°C and 5% CO2 in a CO2 incubator. The cells (6×103 per well) were seeded in a 96-well plate and cultured overnight. Subsequently, the cells were treated with Cilengitide at concentrations of 0, 1, 10, 100, and 1000µg/ml. At 24 hours, 48 hours, and 72 hours after treatment, 10µl of CCK-8 cell counting reagent was added to each well. After incubation at 37°C and 5% CO2 for 2 hours, the absorbance value was measured at a wavelength of 450nm. |
Reaction Conditions | 0, 1, 10, 100, and 1000µg/ml; 24, 48, and 72h |
Applications | Cilengitide treatment reduced cell viability of A375 cells in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Nude rats |
Preparation Method | Cells expressing light chain (LC) 3-green fluorescent protein (GFP) (4×105 cells/5µl PBS) were injected at a rate of 0.5µl/min into the right bregma of nude rats at a distance of 3mm. On the 21st day after tumor cell injection, Cilengitide (4mg/kg) was intraperitoneally injected, and the rats were sacrificed 48 hours later and the brain tissues were removed. The brain tissues were fixed with 10% formalin overnight and placed in a coronal brain tissue slide box, then cut into 2mm thick sections. The 2mm sections containing tumors were frozen in optimal cutting temperature (OCT) tissue blocks and subjected to autophagy-related immunofluorescence analysis. |
Dosage form | 4mg/kg for once; i.p. |
Applications | Cilengitide significantly induced autophagy in the xenograft tumors of rat. |
References: | |
| Cas No. | 188968-51-6 | SDF | |
| 别名 | 西仑吉肽; EMD 121974 | ||
| 化学名 | 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 | ||
| Canonical 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 | ||
| 分子式 | C27H40N8O7 | 分子量 | 588.66 |
| 溶解度 | ≥ 29.433mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6988 mL | 8.4939 mL | 16.9877 mL |
| 5 mM | 339.8 μL | 1.6988 mL | 3.3975 mL |
| 10 mM | 169.9 μL | 849.4 μL | 1.6988 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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