ML334
(Synonyms: LH601A) 目录号 : GC38819
An inhibitor of the Nrf2-Keap1 protein-protein interaction
Cas No.:1432500-66-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ML-334 is an inhibitor of the protein-protein interaction between the transcription factor Nrf2 and its inhibitor Keap1.1 It binds to the Keap1 Kelch domain (IC50 = 1 ?M) to induce dissociation and nuclear translocation of Nrf2 and activation of the antioxidant response element (ARE) in a cell-based assay (EC50 = 12 ?M).
1.Hu, L., Magesh, S., Chen, L., et al.Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interactionBioorg. Med. Chem. Lett.23(10)3039-3043(2013)
| Cas No. | 1432500-66-7 | SDF | |
| 别名 | LH601A | ||
| Canonical SMILES | O=C(C1=CC=CC=C1C2=O)N2C[C@@H]3C4=CC=CC=C4CCN3C([C@H]5[C@H](CCCC5)C(O)=O)=O | ||
| 分子式 | C26H26N2O5 | 分子量 | 446.5 |
| 溶解度 | DMSO: 44.65 mg/mL (100.00 mM); Ethanol: 44.65 mg/mL (100.00 mM) | 储存条件 | Store at 4°C, stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2396 mL | 11.1982 mL | 22.3964 mL |
| 5 mM | 0.4479 mL | 2.2396 mL | 4.4793 mL |
| 10 mM | 0.224 mL | 1.1198 mL | 2.2396 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
体内配方配制方法：取 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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Panaxatriol saponin ameliorates myocardial infarction-induced cardiac fibrosis by targeting Keap1/Nrf2 to regulate oxidative stress and inhibit cardiac-fibroblast activation and proliferation
Free Radic Biol Med 2022 Sep;190:264-275.PMID:35977659DOI:10.1016/j.freeradbiomed.2022.08.016.
Cardiac fibrosis is a common precursor of ventricular dysfunction and heart failure. We investigated the role of oxidative stress in myocardial fibrosis and the protective effect of panaxatriol saponin (PTS) against myocardial infarction (MI)-induced cardiac fibrosis and explored the underlying mechanisms. In vitro, cell viability was tested using a cell counting kit. The reactive oxygen species (ROS) levels including hydrogen peroxide (H2O2) and superoxide anion (O2•-) were determined. Antioxidant enzyme levels were determined by immunofluorescence and Western blotting. Enzyme-linked immunosorbent assays, echocardiography, histological analysis, immunofluorescence staining, and molecular analysis were performed. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation was evaluated by molecular docking and immunoprecipitation. Finally, the mechanism by which PTS inhibits cardiac fibrosis was investigated using the Nrf2 activator ML334 and a small interfering RNA for Nrf2. Ang II-induced differentiation of cardiac fibroblasts was associated with oxidative stress, characterized by upregulation of α-smooth muscle actin, increased reactive oxygen species production, and inhibition of superoxide dismutase-1 and heme oxygenase expression. In addition, PTS improved cardiac function and ameliorated cardiac fibrosis in MI rats. It also reduced Ang II-induced fibroblast differentiation and proliferation, suppressed oxidative stress, and disrupted the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction by directly blocking the Nrf2 binding site in Keap1. Overexpression of Nrf2 by ML334 enhanced the antifibrotic effect of PTS. However, genetic ablation of Nrf2 abrogated the antifibrotic effect of PTS in cardiac fibrosis. Taken together, our findings suggest that Nrf2 has promise as a target and PTS as a therapeutic agent for cardiac fibrosis.
Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction
Bioorg Med Chem Lett 2013 May 15;23(10):3039-43.PMID:23562243DOI:10.1016/j.bmcl.2013.03.013.
A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1-Nrf2 protein-protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure-activity relationships support its use as a lead for our ongoing optimization.