生物活性

• 靶点

  Tubulin IC50:2.4μM

  β-tubulin Kd:0.4μM

• 描述Fosbretabulin Disodium is a cis compound of combretastatin A-4 that can inhibit the tubulin polymerization with IC50 value of 2.4μM . In a breast cancer model, the compound showed no activity loss in the cytotoxicity profile, even with greater toxicity to the endothelial cells as well as HUVECs. The peak plasma level on vascular resistance of the rat P22 tumor was 200μM, which also induced vasomotion during drug infusion. HUVECs treated with 1μM Fosbretabulin Disodium led to microtubule disruption within 30 minutes caused by the absence of polymerized tubulin and an increase in the soluble form. At this concentration, the formation of both abundant actin stress fibers and optimal stress fiber were also found, suggesting an indication of actin cytoskeleton alterations. For cell survival, a significant increasing from 5.5% to 16.9% was observed after exposure to 1μM Fosbretabulin for 2 hours. Furthermore, MLC phosphorylation mediated by the compound attenuated significantly. The sites phosphorylated by MLC phosphorylation peaked at 15 minutes and remained, suggesting a sequential activation of Rho, Rho-kinase, and MLC phosphorylation by the compound. Treatment with Fosbretabulin have led to decrease of antiproliferative activity with IC50 values of 0.0045 μM and 0.0047 μM, respectively, in SKOV3 cells and HeLa cells. In rat A10 cell line, inhibition of microtubule depolymerization (EC50=0.007 μM) could be a reorganization of interphase microtubule network, which caused loss of cellular microtubules, inhibition of colchicine binding and polymerization of tubilin.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HeLa cells	-	Proliferation assay	-	Antiproliferative activity against human HeLa cells by sulforhodamine B assay, IC50=0.0047 μM	20973488
  rat A10 cells	-	Function assay	-	Inhibition of microtubule depolymerization in rat A10 cells assessed as reorganization of interphase microtubule network by indirect immunofluorescence technique, EC50=0.007 μM	20973488
  SKOV3 cells	-	Proliferation assay	-	Antiproliferative activity against human SKOV3 cells by sulforhodamine B assay, IC50=0.0045 μM	20973488

• 动物研究
  剂量	Mice: 150 mg/kg[3] (i.p.) Rat: 3 mg/kg[4] (i.p.),
  给药途径	i.p.

• 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
  NCT00507429	Anaplastic Thyroid Cancer	Phase 2 Phase 3	Terminated(Low rate of subject... more >> accrual) Collapse <<	-	-
  NCT00395434	Tumors	Phase 1	Completed	-	United Kingdom ... more >> Mount Vernon Hospital Northwood, Middlesex, United Kingdom, HA6 2RN Royal Marsden Hospital Sutton, Surrey, United Kingdom, SM2 5PT Collapse <<
  NCT00653939	Tumors	Phase 2	Completed	-	United States, California ... more >> Southbay Oncology Hematology Campbell, California, United States, 95008 Pacific Coast Hematology and Oncology Medical Group Fountain Valley, California, United States, 92708 UCLA Division of Hematology and Oncology Los Angeles, California, United States, 90095 Bay Area Cancer Research Group, LLC Pleasant Hill, California, United States, 94523 United States, Florida Boca Raton Comprehensive Cancer Center Boca Raton, Florida, United States, 21020 United States, Kentucky Kentuckiana Cancer Institute Louisville, Kentucky, United States, 40202 United States, Massachusetts Lahey Clinic Medical Center Burlington, Massachusetts, United States, 01805 United States, New Jersey The Center for Cancer and Hematologic Disease Cherry Hill, New Jersey, United States, 08003 United States, New Mexico San Juan Oncology Associates Farmington, New Mexico, United States, 87401 United States, Ohio Gabrail Cancer Center Canton, Ohio, United States, 44718 The Mark H. Zangmeister Center Columbus, Ohio, United States, 43219 Signal Point Clinical Research Middletown, Ohio, United States, 45042 United States, Virginia Blueridge Cancer Care Salem, Virginia, United States, 24153 United States, Washington Northwest Medical Specialties Tacoma, Washington, United States, 98405 United States, West Virginia Mary Babb Randolph Cancer Center-Clinical Trials Unit Morgantown, West Virginia, United States, 26506 Collapse <<

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