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^[5]. The IC50 values of cilengitide against αvβ3 and αvβ5 are 4.1 nM and 79 nM, respectively^[6]. 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^[7].

• 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)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00006093	Brain and Central Nervous Syst... more >>em Tumors Collapse <<	Phase 1 Phase 2	Completed	-	United States, Alabama ... more >> University of Alabama at Birmingham Comprehensive Cancer Center Birmingham, Alabama, United States, 35294-3300 United States, Florida H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida, United States, 33612-9497 United States, Georgia Emory University Hospital - Atlanta Atlanta, Georgia, United States, 30322 United States, Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231-2410 United States, Massachusetts Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114 United States, Michigan Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, North Carolina Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina, United States, 27157-1082 United States, Ohio Cleveland Clinic Taussig Cancer Center Cleveland, Ohio, United States, 44195 United States, Pennsylvania University of Pennsylvania Cancer Center Philadelphia, Pennsylvania, United States, 19104-4283 United States, Texas University of Texas Health Science Center at San Antonio San Antonio, Texas, United States, 78284-7811 Collapse <<
  NCT00006222	Sarcoma	Phase 1	Terminated(Administratively co... more >>mplete.) Collapse <<	-	United States, California ... more >> University of California San Diego Cancer Center La Jolla, California, United States, 92093-0658 UCSF Cancer Center and Cancer Research Institute San Francisco, California, United States, 94115-0128 United States, Tennessee Vanderbilt Cancer Center Nashville, Tennessee, United States, 37232-6838 Collapse <<
  NCT00022113	Unspecified Adult Solid Tumor,... more >> Protocol Specific Collapse <<	Phase 1	Completed	-	United States, Colorado ... more >> University of Colorado Denver, Colorado, United States, 80217-3364 Collapse <<

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