Biological Activity
Cilengitide is a potent and selective integrin inhibitor for αvβ3 and αvβ5 receptor, with IC50s of 4 and 79 nM, respectively.
In Vitro
Cilengitide (EMD 121974) is the αvβ3 and αvβ5 integrin receptor antagonist. In cell adhesion studies assessing the human melanoma M21 or UCLA-P3 human lung carcinoma cell lines, Cilengitide inhibits integrin-mediated binding to vitronectin with IC50s of 0.4 and 0.4 μM[1]. In vitro treatment of Cilengitide, at a concentration greater than 1 µM, shows concentration- and time-dependent cytotoxic effects. However, lower doses of Cilengitide monotherapy (0.1 and 0.5 µM) does not elicit the effective death of the both U87MG and U251MG cells. Significant cytotoxic effects are observed in the U87MG cells with the addition of 1 µM Cilengitide in combination with Belotecan monotherapy at concentration of 6.25 nM. Higher concentrations of Cilengitide (5 and 25 µM) does not significantly increase cell death in the U87MG and U251MG compare to a lower concentration of Cilengitide (1 µM)[2].
In Vivo
In nude mice bearing M21-L melanoma tumors, Cilengitide dose i.p. at 10, 50, and 250 μg three times per week 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[2]. In the rat model studied, the systemic pharmacokinetics of i.p. Cilengitide are not affected by ILP with Cilengitide alone or ILP with Cilengitide plus Melphalan, TNF or both. Systemic Cilengitide levels reach around 20 µg/mL (approximately 35 µM) within 10 min of i.p. administration and continued to rise to approximately 40 µg/mL (approximately 70 µM) in the first hour. Thereafter Cilengitide levels in serum dropped with an elimination half-life of 2.1 hr[3].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.