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.