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]。