生物活性

• 靶点

  Integrin αvβ3 IC50:4.1nM

  Integrin αvβ5 IC50:79nM

• 描述Integrins are heterodimeric transmembrane receptors involved in a wide range of cancer cell activities. Cilengitide is a selective and potent inhibitor of αv integrins that blocks the ligation of αvβ3 and αvβ5 integrins to provisional matrix proteins. The IC50 values of cilengitide against αvβ3 and αvβ5 are 4.1 nM and 79 nM, respectively. In primary human brain capillary endothelial cells (BCECs), incubation with 1 μg/mL cilengitide for 1h decreased cell adhesion to vitronectin. When cilengitide was added 1h after the attachment of BCECs to vitronectin, the detachment occurred in a dose-dependent manner, and the significant detachment was observed at the concentration of 10 μg/mL or higher. In αv-integrin-expressing tumor cell lines U87MG and DAOY, the exposure of 25 μg/ml cilengitide for 24h led to a significant increase in apoptosis compared to cells treated with control peptide. In a mouse xenograft model established by injecting αv-positive melanoma cells into the forebrain, Cilengitide treatment resulted in an average survival of 36.5 days compared to 17.3 days in the control peptide-treated animals.

• 动物研究
  剂量	Mice: 2.5 mg/kg[3] (i.v.) Monkey: 2 mg/kg[3] (i.v.) Nude Mice: 75 mg/kg[4] (i.p.)
  给药途径	i.v.
  动物药代数据	Animal Mice[3] Dose 1340 ng eq/ml (male) 2840 ng eq/ml (female) Administration i.v. T1/2 0.32 h (male) 0.30 h (female) T1/2β 0.39 h (male) 0.31 h (female) CL 5.68 L/h/kg (male) 3.20 L/h/kg (female) Vdss 1.6 L/kg (male) 0.56 L/kg (female) AUC0→∞ 440 ng/ml/h (male) 781 ng/ml/h (female)