Cilengitide, a
cyclic RGD pentapeptide, is currently in clinical phase III for treatment of
glioblastomas and in phase II for several other
tumors. This
drug is the first anti-angiogenic small molecule targeting the
integrins αvβ3, αvβ5 and αvβ1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in
c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference
peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This
cyclic peptide was later modified by N-methylation of one
peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This
peptide was then dubbed
Cilengitide and is currently developed as
drug by the company Merck-Serono (Germany). This article describes the chemical development of
Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in
cancer treatment can be further increased by combination with "classical" anti-
cancer therapies. Several clinical trials in this direction are under investigation.