Cilengitide is 'n gecycliseerde pentapeptied peptidomimetikum wat ontwerp is om mee te ding vir die arginien-glisien-asparaginsuur (RGD) peptiedvolgorde wat integrien-ligand binding reguleer. Cilengitide blokkeer selektief en kragtig die afbinding van die αvβ3 en αvβ5 integrine na voorlopige matriksproteïene soos vitronektien, fibronektien, fibrinogeen, von Willebrand faktor, osteopontien, en ander. Cilegitide inhibeer angiogenese in vitro. 10 μM Cilengitide completely inhibits attachment of BAE, BME and HUVE cells on vitronectin and fibronectin. Cilengitide inhibits in vitro angiogenesis of BAE cells on three-dimensional collagen and fibrin gels pretreated with FGF-2(or VEGF-A) with IC50 of 15 μM and 8 μM, 4 μM and 3 μM, respectively.Cilengitide blocks proliferation and induces apoptosis of endothelial cells as well as differentiation of human endothelial precursor cells (EPCs). 50 μg/mL Cilengitide completely inhibits the proliferation of human microvascular endothelial cell line HMEC-1 and leads to apoptosis in ~30% cells. 1.0 μM Cilengitide treating for 9 days inhibits the proliferation of EPCs by nearly 40%. 1 μM Cilengitide inhibits the differentiation of EPCs by more than 80% at 14 days. Cilengitide inhibits adhesion and induces apoptosis of tumor cells. 25 μg/mL Cilengitide causes detachment of DAOY cells (medulloblastoma) and U87MG cells (glioblastoma) from vitronectin and tenascin by more than 60%. 25 μg/mL Cilengitide induces a nearly 50% apoptosis rate of these cells
Cilengitide is activity against tumor growth and angiogenesis as single-agent. 100 μg Cilengitide induces a significant decrease in the number of CD 31+ vessels seen in tumors (2/high-power field) compared with control tumors (56/high-power field). 100 μg Cilengitide increases cellular apoptosis in the brain tumors of animals (2.2% apoptotic cells/high-power field) compared with those receiving the inactive peptide (1.7% cells/high-power field). Cilengitide treatment results in prolonged survival of the mice bearing melanoma xenografts M21 compared with control treatment group. (36.5 vs 17.3 days). Cilengitide kan die terapeutiese voordeel wat met sitotoksiese middels geassosieer word, vergroot, insluitend chemoterapie en bestralingsterapie in tumormodelle. Cilengitide (250 mg/dosis) alleen verander nie tumorgroei van borskankerxenotransplantate in vergelyking met onbehandelde muise nie, maar gekombineerde modaliteit RIT (CMRIT) met behulp van RIT en ses dosisse Cilengitide (250 mg/dosis) verhoog die doeltreffendheid van behandeling, met die genesingstempo vir muise wat slegs RIT ontvang wat toeneem vanaf 15 aan 53%. CMRIT verhoog aansienlik apoptose van tumor- en endoteelselle 5 days, en verminder tumorproliferasie.
