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].
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].
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