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Bardoxolone methyl

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Chemical Structure| 218600-53-4 同义名 : RTA 402;NSC 713200;CDDO-Me;TP-155;CDDO Methyl ester
CAS号 : 218600-53-4
货号 : A142891
分子式 : C32H43NO4
纯度 : 98%
分子量 : 505.688
MDL号 : MFCD11983137
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(49.44 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

4%DMSO+30% PEG300+5% Tween+61%water 2.5 mg/mL

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
细胞系 浓度 检测类型 检测时间 活动说明 数据源
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
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 ... 展开 >> Type 2 Diabetes 收起 << Phase 1 Terminated(IDMC recommendation... 展开 >> for safety concerns) 收起 << - -
NCT01576887 End-Stage Renal Disease ... 展开 >> Type 2 Diabetes Mellitus 收起 << Phase 2 Withdrawn(IDMC recommendation ... 展开 >>for safety concerns) 收起 << October 2013 -
NCT00529113 Pancreatic Neoplasms ... 展开 >> Pancreatic Cancer 收起 << Phase 1 Phase 2 Terminated(To pursue other ind... 展开 >>ications) 收起 << - United States, Colorado ... 展开 >> 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 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.98mL

0.40mL

0.20mL

9.89mL

1.98mL

0.99mL

19.77mL

3.96mL

1.98mL
参考文献

[1]Reisman SA, et al. Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney. J Am Soc Nephrol. 2012 Aug 2.

[2]McCullough PA, et al. Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl. Drug Des Devel Ther. 2012;6:141-9.