Home NF-κB IκB/IKK inhibitor - Ferroptosis inhibitor - Nrf2 activator - Apoptosis related activator - Autophagy activator - NF-κB inhibitor Bardoxolone Methyl For research use only.

Bardoxolone Methyl

Synonyms: RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me

Bardoxolone Methyl (RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me) is an IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities; Also a potent Nrf2 activator and nuclear factor-κB (NF-κB) inhibitor. Bardoxolone Methyl abrogates ferroptosis. Bardoxolone methyl induces apoptosis and autophagy in cancer cells.

Bardoxolone Methyl Chemical Structure

Bardoxolone Methyl Chemical Structure

CAS No. 218600-53-4

Purity & Quality Control

Bardoxolone Methyl Related Products

Signaling Pathway

IκB/IKK Signaling Pathways

IκB/IKK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MCF-7 Function assay Inhibitory concentration against proliferation of MCF-7 (ER Positive) breast cancer cells, IC50=0.05μM 15369396
BMDM Cytotoxicity assay 24 hrs Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs, MNTD=0.5μM 22533790
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
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
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
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=4.99μM 24685545
B16F10 Cytotoxicity assay 48 hrs Cytotoxicity against mouse B16F10 cells after 48 hrs by MTT assay, IC50=5.85μM 24685545
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
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 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
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
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
RAW264.7 Anti-inflammatory assay Anti-inflammatory activity in mouse RAW264.7 cells assessed as inhibition of nitric oxide production, IC50=4μM 28754470
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
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 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
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description Bardoxolone Methyl (RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me) is an IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities; Also a potent Nrf2 activator and nuclear factor-κB (NF-κB) inhibitor. Bardoxolone Methyl abrogates ferroptosis. Bardoxolone methyl induces apoptosis and autophagy in cancer cells.
Features The only IKKβ inhibitor in clinical use for solid tumors, type 2 diabetes, and chronic kidney disease. An orally-available antioxidant inflammation modulator.
Targets
IKK [3]
(Cell-free assay)		 Ferroptosis [7] Nrf2 [6] NF-κB [6]
In vitro
In vitro

Bardoxolone Methyl exhibits potent inhibitory activities against production of nitric oxide induced by interferon-Ƴ in mouse macrophages with IC50 of 0.1 nM. [1] Bardoxolone Methyl decreases the viability of leukemic HL-60, KG-1, and NB4 cells with IC50 of 0.4, 0.4, and 0.27 μM, respectively. CDDO-Me induces pro-apoptotic Bax protein, inhibits the activation of ERK1/2, and it blocks Bcl-2 phosphorylation, which contributes to the induction of apoptosis. [2] Bardoxolone Methyl potently inhibits both constitutive and inducible NF-kappaB activated by TNF, interleukin (IL)-1beta, phorbol ester, okadaic acid, hydrogen peroxide, lipopolysaccharide, and cigarette smoke. [3]
Kinase Assay IKK assay
To determine the effect of CDDO-Me on TNF-induced IKK activation, IKK is analyzed. Briefly, the IKK complex from whole-cell extracts was precipitated with antibody against IKKα and IKKβ and then treated with protein A/G-Sepharose beads. After 2 hours, the beads are washed with lysis buffer and then resuspended in a kinase assay mixture containing 50 mmol/L HEPES (pH 7.4), 20 mmol/L MgCl2, 2 mmol/L DTT, 20 μCi [γ-32P]ATP, 10 μmol/L unlabeled ATP, and 2 μg of substrate glutathione S-transferase-IκBα (amino acids 1-54). After incubation at 30°C for 30 minutes, the reaction is terminated by boiling with SDS sample buffer for 5 minutes. Finally, the protein is resolved on 10% SDS-PAGE, the gel is dried, and the radioactive bands are visualized with a Storm820. To determine the total amounts of IKK-α and IKK-β in each sample, 50 μg of whole-cell proteins are resolved on 7.5% SDS-PAGE, electrotransferred to a nitrocellulose membrane, and then blotted with either anti-IKK-α or anti-IKK-β antibody.
Cell Research Cell lines HL-60, KG-1, and NB4 cells
Concentrations ~5 μM
Incubation Time 72 hours
Method

Leukemic cell lines are cultured at a density of 3.0 × 105 cells/mL, and AML mononuclear cells are cultured at 5 × 105 cells/mL in the presence or absence of indicated concentrations of CDDO-Me. Appropriate amounts of DMSO (final concentration less than 0.05%) are included as control. For cytotoxicity studies, 1 μM ara-C is added to the cultures. After 24 to 72 hours, viable cells are counted with the trypan blue dye exclusion method using a hematocytometer.
Experimental Result Images Methods Biomarkers Images 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
In Vivo
In vivo

Bardoxolone Methyl (60 mg/kg) reduces the number, size, and severity of lung tumors in vivo. [4] Bardoxolone Methyl significantly reduces the in vivo inflammatory cytokine response following LPS challenge, induces HO-1 protein expression in the spleen, and protects mice against lethal-dose LPS. [5]
Animal Research Animal Models Female A/J mice are injected i.p. with vinyl carbamate.
Dosages ~60 mg/kg
Administration Oral gavage
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

Chemical Information & Solubility

Molecular Weight 505.69 Formula

C32H43NO4
CAS No. 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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 26 mg/mL ( (51.41 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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