Bardoxolone Methyl

别名: RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me 中文名称:甲基巴多索隆

Bardoxolone Methyl (RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me) 是一种IKK抑制剂,具有强的促凋亡和抗炎活性。同时还是有效的Nrf2激活剂和NF-κB抑制剂。Bardoxolone Methyl 可抑制铁死亡。Bardoxolone Methyl 在癌细胞中可诱导凋亡和自噬。

Bardoxolone Methyl Chemical Structure

Bardoxolone Methyl Chemical Structure

CAS: 218600-53-4

规格 价格 库存 购买数量
25mg 814.73 现货
200mg 4656.69 现货
1g 12700 现货
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Bardoxolone Methyl相关产品

相关信号通路图

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
RAW264.7 Antioxidant assay 100 nM 18 hrs Antioxidant activity in mouse RAW264.7 cells assessed as inhibition of tBHP-induced ROS production at 100 nM pretreated for 18 hrs before challenge measured after 15 mins by H2DCFA-based flow cytometry 24388806
PANC1343 Antiproliferative assay 300 to 1000 nM 72 hrs Antiproliferative activity against mouse PANC1343 cells at 300 to 1000 nM after 72 hrs by MTT assay 24388806
BMDM Antiinflammatory assay 0.5 uM 1 hr Antiinflammatory activity in C57BL/6 mouse BMDM cells assessed as inhibition of LPS-stimulated TNFalpha production at 0.5 uM pretreated for 1 hr before LPS challenge after 8 to 24 hrs by immunoassay 22533790
HCT8 Function assay 1 uM 24 hrs Inhibition of HIF-1alpha protein expression in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of HIF-1alpha protein expression in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of STAT3 protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of STAT3 protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of AKT protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of AKT protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of ERK protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Function assay 1 uM 24 hrs Inhibition of ERK protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method 25675144
HCT8 Antiproliferative assay 1 uM 72 hrs Antiproliferative activity against human HCT8 cells assessed as inhibition of cell proliferation at 1 uM after 72 hrs by MTT assay 25675144
HCT8 Antiproliferative assay 1 uM 72 hrs Antiproliferative activity against 5-FU resistant human HCT8 cells assessed as inhibition of cell proliferation at 1 uM after 72 hrs by MTT assay 25675144
BEAS2B Function assay 10 uM 6 hrs Activation of Nrf2 in human BEAS2B cells assessed as increase in HO1 gene expression at 10 uM incubated for 6 hrs by qPCR method 26278028
H42E Function assay 0.01 to 30 nM 1 hr Stabilization of NRF2 in rat H42E cells expressing ARE8L at 0.01 to 30 nM after 1 hr by Western blot analysis 26908173
NHBE Cytoprotective assay 0.001 to 0.1 uM 18 hrs Cytoprotective activity in NHBE cells assessed as inhibition of tBHP-induced GSH depletion at 0.001 to 0.1 uM preincubated for 18 hrs followed by tBHP addition for 4 hrs by thiostar dye based fluorescence assay 27031670
NHBE Function assay 100 nM 24 hrs Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as increase in GCLM mRNA expression at 100 nM incubated for 24 hrs in presence of non targeting siRNA by qRT-PCR method 27031670
NHBE Function assay 100 nM 24 hrs Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as increase in NQO1 mRNA expression at 100 nM incubated for 24 hrs in presence of non targeting siRNA by qRT-PCR method 27031670
NHBE Function assay 100 nM 48 hrs Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as induction of NQO1 specific activity at 100 nM incubated for 48 hrs in presence of non targeting siRNA by MTT reduction assay 27031670
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as TNFalpha-induced NFkappaB activation at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by NFkappaB-driven luciferase reporter gene assay 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of iNOS mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of COX2 mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of MCP1 mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an 28994286
intraglomerular mesangial cells Function assay 0.65 mg/kg 12 weeks Renoprotective activity in db/db mouse assessed as increase in number of intraglomerular mesangial cells at 0.65 mg/kg, ip administered trice per week for 12 consecutive weeks measured at 11 weeks post dose by H/E-staining based microscopic analysis 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of COX2 protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of iNOS protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as mitigation of TNFalpha-induced increase in ratio of nuclear to cytosolic p65 at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot 28994286
HEK293 Function assay 200 to 1000 nM 24 hrs Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of MCP1 protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as upregulation of HO-1 mRNA expression at 200 to 1000 nM after 48 hrs by quantitative RT-PCR analysis 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as upregulation of NQO1 mRNA expression at 200 to 1000 nM after 48 hrs by quantitative RT-PCR analysis 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as activation of Nrf2 at 200 to 1000 nM after 48 hrs by ARE-driven luciferase reporter gene assay 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in nuclear to cytosolic Nfr2 ratio at 200 to 1000 nM after 48 hrs by Western blot analysis 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in cytosolic HO-1 levels at 200 to 1000 nM after 48 hrs by Western blot analysis 28994286
HEK293 Function assay 200 to 1000 nM 48 hrs Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in cytosolic NQO1 levels at 200 to 1000 nM after 48 hrs by Western blot analysis 28994286
A549/TR Function assay 2.4 to 9.6 uM 24 hrs Induction of ROS generation in human A549/TR cells at 2.4 to 9.6 uM after 24 hrs by DCFH-DA dye-based flow cytometric analysis 29501947
A549/TR Function assay 4.8 uM 24 hrs Downregulation of Lon expression in human A549/TR cells at 4.8 uM after 24 hrs by Western blot analysis 29501947
B16F10 Cytotoxicity assay 48 hrs Cytotoxicity against mouse B16F10 cells after 48 hrs by MTT assay, IC50=5.85μM 24685545
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=4.99μM 24685545
BMDM Cytotoxicity assay 24 hrs Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs, MNTD=0.5μM 22533790
CCD-841-CoN Antiproliferative assay 72 hrs Antiproliferative activity against human CCD-841-CoN cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.316μM 25675144
HCT8 Antiproliferative assay 72 hrs Antiproliferative activity against 5-FU resistant human HCT8 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.363μM 25675144
HCT8 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT8 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.399μM 25675144
H42E Function assay 24 hrs Induction of NRF2 activation in rat H42E cells expressing ARE8L assessed as reporter transgene activity after 24 hrs by luminescence assay, CD=0.0005μM 26908173
H42E Cytotoxicity assay 24 hrs Cytotoxicity against rat H42E cells expressing ARE8L assessed as cellular ATP level after 24 hrs by Celltiter-Glo luminescent cell viability assay, IC50=1.4μM 26908173
HaCaT-ARE-luc Function assay 6 hrs Activation of Nrf2 (unknown origin) expressed in human HaCaT-ARE-luc cells after 6 hrs by luciferase reporter gene assay, EC50=0.06μM 28753294
NIH/3T3 Function assay 6 hrs Inhibition of TNF-alpha stimulated NF-kappaB (unknown origin) expressed in mouse NIH/3T3 cells after 6 hrs by luciferase reporter gene assay, IC50=1.2μM 28753294
HeLa Function assay 6 hrs Inhibition of IFN-gamma stimulated STAT3 (unknown origin) expressed in human HeLa cells after 6 hrs by luciferase reporter gene assay, IC50=2.38μM 28753294
HEK293 Cytotoxicity assay 24 hrs Cytotoxicity against HEK293 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=2.2μM 28994286
H9c2 Cytotoxicity assay 24 hrs Cytotoxicity against rat H9c2 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=5.2μM 28994286
A549/TR Antiproliferative assay 72 hrs Antiproliferative activity against human A549/TR cells after 72 hrs by MTT assay, IC50=1.703μM 29501947
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=2.074μM 29501947
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.00025μM 30429953
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by SRB assay, IC50=0.28μM 30429953
HCT8 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT8 cells after 72 hrs by SRB assay, IC50=0.29μM 30429953
HCT116 Function assay 8 hrs Inhibition of Bmi1 protein expression in human HCT116 cells after 8 hrs by Western blot analysis 30429953
BEAS2B Function assay 48 hrs Activation of Keap1/Cul3/Nrf2 in human BEAS2B cells assessed as increase in NQO1 levels measured after 48 hrs, EC50=0.00871μM 30626555
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.26μM 31051401
MCF7 Cytotoxicity assay 48 hrs Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.35μM 31051401
A549 Cytotoxicity assay 48 hrs Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.36μM 31051401
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.52μM 31725288
HepG2 Antiproliferative assay 48 hrs Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.52μM 31725288
HOS Antiproliferative assay 48 hrs Antiproliferative activity against human HOS cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.66μM 31725288
MCF7 Antiproliferative assay 48 hrs Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.85μM 31725288
HEK293FT Function assay 24 hrs Inhibition of mouse GOAT expressed in HEK293FT cells co-expressing pre-proghrelin assessed as reduction in ghrelin octanoylation incubated for 24 hrs by ELISA, IC50=0.035μM ChEMBL
MCF-7 Function assay Inhibitory concentration against proliferation of MCF-7 (ER Positive) breast cancer cells, IC50=0.05μM 15369396
RAW264.7 Anti-inflammatory assay Anti-inflammatory activity in mouse RAW264.7 cells assessed as inhibition of nitric oxide production, IC50=4μM 28754470
点击查看更多细胞系数据

生物活性

产品描述 Bardoxolone Methyl (RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me) 是一种IKK抑制剂,具有强的促凋亡和抗炎活性。同时还是有效的Nrf2激活剂和NF-κB抑制剂。Bardoxolone Methyl 可抑制铁死亡。Bardoxolone Methyl 在癌细胞中可诱导凋亡和自噬。
特性 Bardoxolone Methyl是一种口服有效的抗炎症调节剂,唯一用于临床实体瘤,2型糖尿病和慢性肾脏疾病的IKKβ抑制剂。
靶点
IKK [3]
(Cell-free assay)
Ferroptosis [7] Nrf2 [6] NF-κB [6]
体外研究(In Vitro)
体外研究活性

Bardoxolone Methyl作用于小鼠巨噬细胞,对interferon-Ƴ诱导的一氧化氮的产生具有强效的抑制活性,其IC50 为0.1 nM 。[1] Bardoxolone Methyl降低白血病HL-60,KG-1和NB4细胞的生存能力,其IC50分别为 0.4,0.4,和0.27μM。 CDDO-ME诱导促凋亡Bax蛋白表达,抑制ERK1 / 2的活化,并且它抑制Bcl-2的磷酸化,这有助于诱导细胞凋亡。[2] Bardoxolone Methyl可有效地抑制(IL)-1beta, phorbol ester, okadaic acid, hydrogen peroxide, lipopolysaccharide, 和cigarette smoke激活的组成型和可诱导的NF-κB的肿瘤坏死因子。[3]

激酶实验 IKK 试验
对IKK进行分析,以确定CDDO-ME对TNF诱导的IKK活化的效果。简言之,从全细胞提取物的IKK复合物与针对IKKα和IKKβ抗体沉淀,然后用蛋白A / G琼脂糖珠进行处理。 2小时后,用裂解缓冲液清洗珠粒,然后悬浮在含有50 mmol/L HEPES (pH 7.4) 的激酶测定混合物中,20 mmol/L MgCl2,2 mmol / L的DTT,2 mmol/L DTT, 20 μCi [γ-32P]ATP,10 μmol/L未标记的ATP和2 μg谷胱甘肽S-转移酶- IκBα(氨基酸1-54)的底物。在30℃下进行温育30分钟,然后加入SDS缓冲液,沸浴5分钟终止该反应。最后,该蛋白在10%SDS-PAGE凝胶中分离,干燥,用Storm820观察记录放射性条带。为了确定每个样品中的IKK-α和IKK-β的总量,将50 μg的全细胞蛋白在7.5%的SDS-PAGE下解析,电子转移至硝酸纤维素膜上,然后与抗-IKK-α或抗-IKK-β的抗体印迹杂交。
细胞实验 细胞系 HL-60, KG-1, 和 NB4 细胞
浓度 ~5 μM
孵育时间 72 小时
方法

白血病细胞系以3.0 × 105 cells/mL的密度进行培养,同时白血病单核细胞以5 × 105 cells/mL的密度置于存在或不存在显示浓度的CDDO-ME中培养。加入适量的 DMSO(终浓度小于0.05%)作为对照。添加1 μM ara-C到培养基,用以细胞毒性研究。 24至72小时后,用血细胞计数板的台盼蓝染料排除法进行存活细胞计数。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot p-IκBα / IκBα Bcl-xl / Bcl-2 / Bax / Cleaved caspase / Cytochrome C / PARP / Cleaved PARP p-PI3K / PI3K / p-AMPK / AMPK / p-p38 MAPK / p38 MAPK / p-AKT / AKT / p-mTOR / mTOR PTEN / PP2A / PHLPP1 25897966
Immunofluorescence PDI / SDHA c-PARP / Cytochrome C / COX IV 26053096
Growth inhibition assay Cell viability 25733817
体内研究(In Vivo)
体内研究活性

Bardoxolone Methyl(60 mg/kg)体内用药,可减少肺肿瘤的数量,大小和降低严重程度。 [4] Bardoxolone Methyl还可显著降低LPS刺激下的体内炎症因子的反应,诱导脾脏HO-1蛋白表达,对抗致死剂量的LPS保护小鼠。 [5]

动物实验 Animal Models 雌性 A/J 小鼠 腹腔注射 Vinyl carbamate.
Dosages ~60 mg/kg
Administration 口服给药
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02316821 Completed
Chronic Kidney Disease|Type 2 Diabetes
Kyowa Kirin Co. Ltd.
December 2014 Phase 2
NCT02036970 Completed
Pulmonary Arterial Hypertension|Pulmonary Hypertension|Interstitial Lung Disease|Idiopathic Interstitial Pneumonia|Idiopathic Pulmonary Fibrosis|Sarcoidosis|Respiratory Bronchiolitis Associated Interstitial Lung Disease|Desquamative Interstitial Pneumonia|Cryptogenic Organizing Pneumonia|Acute Interstitial Pneumonitis|Idiopathic Lymphoid Interstitial Pneumonia|Idiopathic Pleuroparenchymal Fibroelastosis
Reata a wholly owned subsidiary of Biogen|Biogen
May 31 2014 Phase 2
NCT01598363 Completed
Healthy Volunteers
Reata a wholly owned subsidiary of Biogen|Biogen
June 30 2012 Phase 1
NCT01551446 Withdrawn
Renal Insufficiency Chronic|Diabetes Mellitus Type 2
Reata a wholly owned subsidiary of Biogen|Biogen
April 30 2012 Phase 1
NCT01503866 Completed
Healthy
Reata a wholly owned subsidiary of Biogen|Biogen
December 1 2011 Phase 1

化学信息&溶解度

分子量 505.69 分子式

C32H43NO4

CAS号 218600-53-4 SDF Download Bardoxolone Methyl SDF
Smiles CC1(CCC2(CCC3(C(C2C1)C(=O)C=C4C3(CCC5C4(C=C(C(=O)C5(C)C)C#N)C)C)C)C(=O)OC)C
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 26 mg/mL ( (51.41 mM) ;DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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