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Bardoxolone methyl

Product Name
Bardoxolone methyl
CAS No.
218600-53-4
Chemical Name
Bardoxolone methyl
Synonyms
CDDO-Me;CDDO Methyl Ester;TP-155;CS-322;TP-155C;RTA 402;NSC 713200;MethylCDDO;Methyl-CDDO;Bardoxolone Methyl
CBNumber
CB22514853
Molecular Formula
C32H43NO4
Formula Weight
505.69
MOL File
218600-53-4.mol
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Bardoxolone methyl Property

Melting point:
215-223°C
Boiling point:
600.8±55.0 °C(Predicted)
Density 
1.15
storage temp. 
Refrigerator
solubility 
Chloroform (Slightly), Methanol (Slightly)
form 
Solid
color 
White to Light Brown
InChIKey
WPTTVJLTNAWYAO-KPOXMGGZSA-N
SMILES
C1(=O)[C@@]([C@]2([C@](C)(C=C1C#N)C1[C@@]([C@]3([C@@](C(=O)C=1)([H])[C@]1([C@@](CC[C@](C1)(C)C)(C(OC)=O)CC3)[H])C)(C)CC2)[H])(C)C
CAS DataBase Reference
218600-53-4
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H371May cause damage to organs

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P309+P311IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.

P405Store locked up.

P501Dispose of contents/container to..…

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
5.05308
Product name
CDDO-Me - CAS 218600-53-4 - Calbiochem
Packaging
10MG
Price
$205
Updated
2022/05/15
Cayman Chemical
Product number
11883
Product name
CDDO methyl ester
Purity
≥98%
Packaging
5mg
Price
$58
Updated
2024/03/01
Cayman Chemical
Product number
11883
Product name
CDDO methyl ester
Purity
≥98%
Packaging
1mg
Price
$30
Updated
2023/06/20
Cayman Chemical
Product number
11883
Product name
CDDO methyl ester
Purity
≥98%
Packaging
10mg
Price
$99
Updated
2024/03/01
Cayman Chemical
Product number
11883
Product name
CDDO methyl ester
Purity
≥98%
Packaging
50mg
Price
$319
Updated
2024/03/01
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Bardoxolone methyl Chemical Properties,Usage,Production

Description

Bardoxolone methyl is an antioxidant inflammatory modulator that reversibly interacts with critical free thiol groups of cysteine residues on KEAP-1 and other target proteins, inducing the trans-location of Nrf-2 to the nucleus and the activation of several genes, including glutathione S-transferase, haeme oxygenase, and other components of the cytoprotective response (Thomas et al., 2012). At high doses, bardoxolone methyl may also interact with other proteins, including PPAR-gamma, tubulin, and the kinase activa-tor IKK.

Chemical Properties

White to Off-White Solid

Uses

CDDO Methyl Ester is a synthetic triterpenoid that inhibits IκBα kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor κB-regulated gene products in human leukemic cells. CDDO Methyl Ester is a novel therapeutic agent in the treatment of acute myeloid leukemia and in the treatment of pancreatic cancer as well as other forms of cancer.

Uses

Bardoxolone methyl is an antiinflam-matory drug that activates the Nrf2-Keap1 pathway,resulting in inhibition of the proinflammatory cytokine Nf-κB.
Bardoxolone methyl (BARD, CDDO-ME, RTA-402) is an orally bioavailable semi-synthetic triterpenoid compound based of the scaffold of oleanolic acid. It was developed by Reata Pharmaceuticals as an activator of the Nrf2 antioxidant pathway. It has been tested in clinical trials for kidney disease, pulmonary hypertension, and cancer.

Definition

ChEBI: Bardoxolone methyl is a member of cyclohexenones.

Clinical Use

Bardoxolone methyl is a synthetic compound derived from oleanolic acid,whichactivates the Keap1-Nrf2 pathway and regulates inflammation in the kidney. In the Bardoxolone Methyl Treatment: Renal Function in CKD/Type 2 Diabetes (BEAM)study,patients with CKD and diabetes wererandomly assigned to receive either bardoxolone methyl or placebo for 52 weeks.Bardoxolone methyl significantly increased the mean eGFR compared with placebo at 24 weeks. The improvement lasted for another 28 weeks. Adverse events, particularly muscle spasms,were more frequent in the bardoxolone methyl group.The Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: the Occurrence of Renal Events study was designed to confirm the findings of the BEAM study. Unfortunately the study was prematurely stopped owing to unacceptable high rates of cardiovascular events in patients treated with bardoxolone methyl at a medianduration of 7 months,and no benefit wasobserved about the risk of ESRD. The beneficial effects of an Nrf2 agonist called dh404, which is a derivative of bardoxolone methyl, via reduction in inflammation and oxidative stress but only at low doses have recently been shown in mice. This finding rekindles the interests on renoprotection via activation of the Nrf2 pathway in DKD.

Enzyme inhibitor

This oleanane triterpenoid (FW = 505.70 g/mol; CAS 218600-53-4; Solubility: 1 mg/mL DMSO; <1 mg/mL H2O), also known as RTA 402, TP- 155, NSC 713200, CDDO Methyl Ester, and 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oic acid methyl ester, targets Inhibitor of nuclear factor Kappa-B Kinase subunit b, or IKKb, a key component of the cytokine activated intracellular signaling pathway that triggers immune responses. Significantly, CDDO methyl ester inhibits proliferation of myeloid leukemia cells, inducing both differentiation and apoptosis. CDDO-Me induces loss of mitochondrial membrane potential, induction of caspase-3 cleavage, increase in annexin V binding, and DNA fragmentation – all suggesting induction of apoptosis. CDDO-Me induces pro-apoptotic Bax protein that preceded caspase activation. CDDO-Me also inhibits ERK1/2 activation, as indicated by inhibition of mitochondrial ERK1/2 phosphorylation and blocking of Bcl-2 phosphorylation, rendering the latter less anti-apoptotic. CDDO-Me inhibits NF-kB through inhibition of IkBa kinase, resulting in the suppression of expression of NF-kB-regulated gene products (Readouts: IAP2, cFLIP, TRAF1, survivin, and Bcl-2) as well as inhibition of proliferation (Readouts: cyclin d1 and c-myc), and angiogenesis (Readouts: VEGF, Cox-2, and MMP-9). CDDO-Me thus enhances apoptosis induced by TNF and chemotherapeutic agents. Bardoxolone methyl exhibits potent pro-apoptotic and anti-inflammatory activity, potently inhibiting interferon γ-induced nitric oxide synthesis in mouse macrophages, IC50 = 0.1 nM. Bardoxolone methyl pretreatment uniquely confers protection against lipopolysaccharide (LPS) challenge by modulating the in vivo immune response to LPS, indicating that it represents a novel oral agent for use in LPS-mediated inflammatory diseases. Significantly, a number of well-recognized naturally occurring or synthetic anti-inflammatory compounds possessing a Michael-type acceptor (e.g., thymoquinone (TQ), the paracetamol metabolite NAPQI, the 5-LO inhibitor AA-861, and bardoxolone methyl) are all direct covalent 5-LO enzyme inhibitors that target the catalytically relevant Cysteines 416 and 418. Their actiom as irreversible Michael acceptor moietied that interact with required cysteines of proteins/enzymes may expain why they are effective and sustained enzyme activity modulators.

target

antioxidant inflammation

storage

Store at -20°C

Mode of action

Bardoxolone Methyl is the methyl ester form of bardoxolone, a synthetic triterpenoid compound with potential antineoplastic and anti-inflammatory activities. Bardoxolone blocks the synthesis of inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), two enzymes involved in inflammation and carcinogenesis. This agent also inhibits the interleukin-1 (IL-1)-induced expression of the pro-inflammatory proteins matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13) and the expression of Bcl-3; Bcl-3 is an IL-1-responsive gene that preferentially contributes to MMP-1 gene expression.

Bardoxolone methyl Preparation Products And Raw materials

Raw materials

Preparation Products

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Bardoxolone methyl Suppliers

ShangHai Caerulum Pharma Discovery Co., Ltd.
Tel
18149758185 18149758185
Email
sales-cpd@caerulumpharma.com
Country
China
ProdList
3466
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58
Shanghai Jingjinchem Co., Ltd.
Tel
021-13817626287 13817626287
Fax
QQ1094777898
Email
1094777898@qq.com
Country
China
ProdList
110
Advantage
55
Finetech Industry Limited
Tel
027-87465837 19945049750
Fax
027-8777-2287
Email
sales@finetechnology-ind.com
Country
China
ProdList
9649
Advantage
58
Olix (Shanghai) Pharmaceutical Technology Co., Ltd
Tel
17316404525
Email
209533805@qq.com
Country
China
ProdList
9787
Advantage
58
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
WUHAN SUN-SHINE BIO-TECHNOLOGY Co., Ltd.
Tel
17702719238 17702719238
Email
sales@sun-shinechem.com
Country
China
ProdList
960
Advantage
64
Shanghai Longsheng chemical Co.,Ltd.
Tel
021-58099652-8005 13585536065
Fax
021-58099609
Email
bin.wu@shlschem.com
Country
China
ProdList
9809
Advantage
59
Nanjing Chemlin Chemical Co., Ltd
Tel
025-83697070
Fax
+86-25-83453306
Email
info@chemlin.com.cn
Country
China
ProdList
19172
Advantage
64
Chemsky(shanghai)International Co.,Ltd.
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
32321
Advantage
50

218600-53-4, Bardoxolone methylRelated Search:


  • NSC 713200
  • Bardoxolone Me ester
  • Bardoxolone Methyl (RTA 402)
  • Oleana-1,9(11)-dien-28-oic acid, 2-cyano-3,12-dioxo-, methyl ester
  • TP-155
  • Methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester
  • 2-Cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid methyl ester
  • BARDOXOLONE METHYL; CDDO METHYL ESTER; CDDOME; NSC 713200; RTA 402; RTA-402; RTA402; TP-155; TP155; TP 155
  • (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-methyl 11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylate
  • MethylCDDO
  • Methyl-CDDO
  • RTA-402; NSC-713200; TP-155C; METHYL-CDDO; METHYLCDDO;BARDOXOLONE METHYL
  • TP-155C
  • BARDOXOLONE METHYL;NSC 713200; RTA 402
  • (4aS,6aR,6bS,8aR,12aS,14bS)-Methyl 11-cyano-2,2,6a,6b,9,9,12a-he
  • CDDO Methyl Ester
  • (4aS,6aR,6bS,8aR,12aS,14bS)-methyl 11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylate
  • Bardoxolone Methyl
  • 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester
  • RTA 402
  • CDDO-Me
  • Bardoxolone methyl (NSC-713200)
  • Bardoxolone methyl, 98%, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)
  • Methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate
  • (4aR,6aR,6bS,8aR,12aR,14bR)-Methyl 11-cyano-2,2,6a,6b,9,9,12a-heptaMethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylate
  • methyl (4aS,6aR,6bS,8aR,12aS,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylate
  • (4aS,6aR,6bS,8aR,12aS,14bS)-methyl 11-cyano-2,2,6a
  • CS-322
  • methyl (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylate
  • CDDO-Me - Bardoxolone methyl | RTA 402
  • methyl (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-hexadecahydropicene-4a(2H)-carboxylate
  • Bardoxolone methyl USP/EP/BP
  • Bardoxolone methyl-13C2 D3 15N
  • CDDO Methyl Ester Bardoxolone methyl
  • Abametapir Impurity 21
  • 218600-53-4
  • NF-kB
  • Apoptosis
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Protein Kinase Inhibitors and Activators
  • Inhibitor
  • Inhibitors