Cilengitide

Cilengitide (EMD 121974) is a cyclic pentapeptide (5 amino acids) and a first-in-class integrin antagonist. It was developed by Merck KGaA in collaboration with the Technical University of Munich. The peptide contains the RGD (arginine-glycine-aspartic acid) motif, a sequence recognized by integrin receptors. Cilengitide is structurally derived from the cyclic peptide c(RGDfV) with a critical modification: incorporation of N-methyl valine at position 5, yielding cyclo(RGDf-NMe-V). This modification dramatically enhances both metabolic stability and receptor binding affinity. It is the most advanced integrin inhibitor in clinical development, displaying sub-nanomolar antagonistic activity against αvβ3 integrin (IC50 = 4.1 nM) and αvβ5 integrin (IC50 = 79 nM), with approximately 10-fold selectivity over gpIIb/IIIa.