生物活性

• 描述The NF-kB pathway plays a key role in multiple cellular processes, including immune signaling, inflammation, development, proliferation and survival. NF-κB suppression occurred through inhibition, activation, phosphorylation and degradation of IκB-α, p65 phosphorylation, p65 nuclear translocation, and NF-κB-mediated reporter gene transcription. Bardoxolone Methyl is a synthetic triterpenoid based on naturally occurring ursolic and oleanolic acids and can inhibit both constitutive and inducible NF-κB through inhibition of IκB-α kinase. Pre-treatment with 1μM Bardoxolone Methyl for 8h could inhibit TNF-induced IκB-α activation, IκB-α phosphorylation within 30 minutes, and subsequently p65 phosphorylation and p65 nuclear translocation in KBM-5cells, without direct effect on IKK. Consistent with this, as the expression of COX-2, MMP-9 and VEGF is regulated by NF-κB, 1μM Bardoxolone Methyl could inhibit TNF-induced expression of this three proteins in a time-dependent manner in KBM-5 cells pre-treated with Bardoxolone Methyl for 8h. Bardoxolone Methyl could enhance the apoptosis induced by TNF or chemotherapeutic agents, including Taxol, 5-fluorouracil and doxorubicin, through inhibition of NF-κB activation in KBM-5 cells. Oral administration of 10 mg/kg Bardoxolone Methyl for 21 weeks could prevent the colon inflammation induced by high fat diet in mice through its effect on regulation of macrophages, NF-κB, cytokines, Cox2 and Ki67, fat deposition and microflora.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  C57BL/6 mouse BMDM cells	-	Cytotoxic assay	24 h	Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs	22533790
  human CCD-841-CoN cells	-	Proliferation assay	72 h	Antiproliferative activity against human CCD-841-CoN cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.316 μM	25675144
  human HCT8 cells	-	Proliferation assay	72 h	Antiproliferative activity against human HCT8 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.399 μM	25675144

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• 动物研究
  剂量	Mice[3] (i.p.): min = 1.25 mg/kg, max = 10 mg/kg Monkeys[4] (p.o.): 30 mg/kg
  给药途径	i.p., p.o.

• 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
  NCT01500798	Chronic Kidney Disease ... more >> Type 2 Diabetes Collapse <<	Phase 1	Terminated(IDMC recommendation... more >> for safety concerns) Collapse <<	-	-
  NCT01576887	End-Stage Renal Disease ... more >> Type 2 Diabetes Mellitus Collapse <<	Phase 2	Withdrawn(IDMC recommendation ... more >>for safety concerns) Collapse <<	October 2013	-
  NCT00529113	Pancreatic Neoplasms ... more >> Pancreatic Cancer Collapse <<	Phase 1 Phase 2	Terminated(To pursue other ind... more >>ications) Collapse <<	-	United States, Colorado ... more >> Rocky Mountain Cancer Center (US Oncology) Denver, Colorado, United States United States, Florida Cancer Centers of Florida (US Oncology) Ocoee, Florida, United States United States, Indiana Central Indiana Cancer Centers (US Oncology) Indianapolis, Indiana, United States United States, Texas Sammons Cancer Center (US Oncology) Dallas, Texas, United States, 75246 United States, Washington Northwest Cancer Specialist- Vancouver Cancer Specialist (US Oncology) Vancouver, Washington, United States Collapse <<

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