Bardoxolone methyl
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- CAS-Nr.
- 218600-53-4
- Englisch Name:
- Bardoxolone methyl
- Synonyma:
- CDDO-Me;CDDO Methyl Ester;TP-155;CS-322;TP-155C;RTA 402;MethylCDDO;NSC 713200;Methyl-CDDO;Bardoxolone Methyl
- CBNumber:
- CB22514853
- Summenformel:
- C32H43NO4
- Molgewicht:
- 505.69
- MOL-Datei:
- 218600-53-4.mol
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Bardoxolone methyl Eigenschaften
- Schmelzpunkt:
- 215-223°C
- Siedepunkt:
- 600.8±55.0 °C(Predicted)
- Dichte
- 1.15
- storage temp.
- Refrigerator
- L?slichkeit
- Chloroform (Slightly), Methanol (Slightly)
- Aggregatzustand
- Solid
- Farbe
- 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 Datenbank
- 218600-53-4
Sicherheit
- Risiko- und Sicherheitserkl?rung
- Gefahreninformationscode (GHS)
| Bildanzeige (GHS) |
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| Alarmwort |
Warnung |
| Gefahrenhinweise |
| Code |
Gefahrenhinweise |
Gefahrenklasse |
Abteilung |
Alarmwort |
Symbol |
P-Code |
| H371 |
Kann die Organe sch?digen. |
Spezifische Zielorgan-Toxizit?t |
Kategorie 2 |
Warnung |
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P260, P264, P270, P309+P311, P405,P501 |
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| Sicherheit |
| P260 |
Dampf/Aerosol/Nebel nicht einatmen. |
| P264 |
Nach Gebrauch gründlich waschen. |
| P264 |
Nach Gebrauch gründlich waschen. |
| P270 |
Bei Gebrauch nicht essen, trinken oder rauchen. |
| P309+P311 |
BEI Exposition oder Unwohlsein: GIFTINFORMATIONSZENTRUM oder Arzt anrufen. |
| P405 |
Unter Verschluss aufbewahren. |
| P501 |
Inhalt/Beh?lter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen. |
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Bardoxolone methyl Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
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.
Chemische Eigenschaften
White to Off-White Solid
Verwenden
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.
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.
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 Upstream-Materialien And Downstream Produkte
Upstream-Materialien
218600-51-2
(4aS,6aR,6bS,12aS,14aR,14bR)-Methyl 11-cyano-10-hydroxy-2,2,6a,6b,9,9,12a-heptaMethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,12,12a,14,14a,14b-octadecahydropicene-4a-carboxylate
(4aS,6aR,6bS,12aS,14aR,14bR,Z)-Methyl 11-(hydroxyMethylene)-2,2,6a,6b,9,9,12a-heptaMethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-4a-carboxylate
Oleana-1,12-dien-28-oic acid, 3-oxo-, methyl ester
(4aS,6aR,6bS,10R,12aS,14aR,14bR)-Methyl 10-hydroxy-2,2,6a,6b,9,9,12a-heptaMethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-4a-carboxylate
3β-Hydroxyolean-12-en-28-sure
(4aS,6aR,6bS,8aR,12aR,14bS)-methyl 11-bromo-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
(4aS,6aR,6bS,10S,12aS,14aR,14bR)-Methyl 10-acetoxy-2,2,6a,6b,9,9,12a-heptaMethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-4a-carboxylate
(4aS,6aR,6bS,13aS,15aR,15bR)-Methyl 2,2,6a,6b,9,9,13a-heptaMethyl-15-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,13,13a,15,15a,15b-octadecahydropiceno[2,3-d]isoxazole-4a-carboxylate
Olean-9(11)-en-28-oic acid, 3,12-dioxo-, methyl ester (9CI)
Methanol
Downstream Produkte
Bardoxolone methyl Anbieter Lieferant Produzent Hersteller Vertrieb H?ndler.
Global( 202)Lieferanten
- 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
- (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
- (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
- 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
- (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
- BARDOXOLONE METHYL; CDDO METHYL ESTER; CDDOME; NSC 713200; RTA 402; RTA-402; RTA402; TP-155; TP155; TP 155
- Bardoxolone methyl (NSC-713200)
- Bardoxolone methyl, 98%, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)
- 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
- CDDO Methyl Ester
- CDDO-Me
- 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
