バルドキソロンメチル

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Warning

• 危険有害性情報

  H371：臓器の障害のおそれ

• 注意書き

  P260：粉じん/煙/ガス/ミスト/蒸気/スプレーを吸入しないこ と。

  P264：取扱い後は皮膚をよく洗うこと。

  P264：取扱い後は手や顔をよく洗うこと。

  P270：この製品を使用する時に、飲食または喫煙をしないこ と。

  P309+P311：暴露したとき、または気分が悪い時：医師に連絡するこ と。

  P405：施錠して保管すること。

  P501：内容物/容器を．．．に廃棄すること。

バルドキソロンメチル 化学特性,用途語,生産方法

• 効能

  抗炎症薬

• 説明

  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.

• 化学的特性

  White to Off-White Solid

• 使用

  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.

• 臨床応用

  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.

バルドキソロンメチル 上流と下流の製品情報

バルドキソロンメチル 生産企業

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バルドキソロンメチル スペクトルデータ(¹HNMR)

218600-53-4, バルドキソロンメチル キーワード