ML334
(Synonyms: LH601A) 目录号 : GC38819
ML334是一种有效的NRF2细胞渗透性激活剂。
Cas No.:1432500-66-7
Sample solution is provided at 25 µL, 10mM.
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ML334 is a potent, cell-permeable activator of NRF2. It achieved through the inhibition of the Keap1-NRF2 protein-protein interaction. It demonstrates a binding affinity to Keap1 with a dissociation constant (Kd) of 1 μM in competitive surface plasmon resonance (SPR) assays. Furthermore, ML334 competes with an Nrf2 peptide, exhibiting an IC50 of 1.6 μM in fluorescence polarization (FP) assays[1-3].
ML334(100 μM; 3 hours) induces the expression and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) in HEK293 cells. Meanwhile, ML334 treatment induced the expression of HO-1 and TRX1 proteins in HEK293 cells [4].ML334-induced (50 μM; 48 hours) overexpression of Nrf2 enhances the antifibrotic effect of panaxatriol saponin (PTS) in cardiac fibroblasts[5].
[1]. Hu L, Magesh S, Chen L, Wang L, Lewis TA, Chen Y, Khodier C, Inoyama D, Beamer LJ, Emge TJ, Shen J, Kerrigan JE, Kong AN, Dandapani S, Palmer M, Schreiber SL, Munoz B. et,al. 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. doi: 10.1016/j.bmcl.2013.03.013. Epub 2013 Mar 14. PMID: 23562243; PMCID: PMC3648997.
[2]. Shen J, Magesh S, et,al. Enantiomeric characterization and structure elucidation of LH601A using vibrational circular dichroism spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc. 2018 Mar 5;192:312-317. doi: 10.1016/j.saa.2017.11.033. Epub 2017 Nov 21. PMID: 29172127; PMCID: PMC10544735.
[3]. Wang L, Lewis T. et,al. The identification and characterization of non-reactive inhibitor of Keap1-Nrf2 interaction through HTS using a fluorescence polarization assay. 2012 Dec 17 [updated 2013 Sep 16]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 24260785.
[4]. Wen X, Thorne G, et,al. Activation of NRF2 Signaling in HEK293 Cells by a First-in-Class Direct KEAP1-NRF2 Inhibitor. J Biochem Mol Toxicol. 2015 Jun;29(6):261-6. doi: 10.1002/jbt.21693. Epub 2015 Feb 12. PMID: 25683455; PMCID: PMC4713195.
[5]. Yao H, He Q, et,al. 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. doi: 10.1016/j.freeradbiomed.2022.08.016. Epub 2022 Aug 14. Erratum in: Free Radic Biol Med. 2023 Jun;202:34. PMID: 35977659.
ML334是一种有效的NRF2细胞渗透性激活剂。通过抑制Keap1-NRF2蛋白-蛋白相互作用实现。在竞争表面等离子体共振(SPR)实验中，它与Keap1具有1 μM的解离常数(Kd)。此外，ML334与Nrf2肽竞争，IC50为1.6 μM[1-3]。
ML334(100μM;3h)诱导HEK293细胞中NRF2的表达和核易位。同时，ML334处理诱导 HEK293 细胞中的 HO-1 和 TRX1 蛋白表达[4]。ML334诱导(50 μM;48h)Nrf2的过表达增强了panaxatriol saponin (PTS)在心脏成纤维细胞中的抗纤维化作用[5]。
| Cell experiment [1]: | |
Cell lines | HEK293 cells |
Preparation Method | Cells were treated with ML334 for 3 hours. |
Reaction Conditions | 100 μM; 3 hours |
Applications | ML334 enhances the expression and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) in HEK293 cells. |
Competitive SPR assay [2]: | |
Animal models | |
Preparation Method | A biotinylated 16mer peptide from the Keap1 binding region of Nrf2 was captured by streptavidin on a CM5 chip surface (300 RU). A solution containing 40 nM of the Kelch domain of Keap1 protein, preincubated with ML334, was injected over the immobilized Nrf2 peptide surface. The assay was conducted at 25℃ with a flow rate of 50 μL/min, allowing for a 1-minute association time and a 3-minute dissociation time. The sensor chip surface was regenerated with 1M NaCl at a flow rate of 100 μL/min for 1 minute, followed by two consecutive 1-minute washes with the running buffer at the same flow rate. The binding signal of Keap1 to Nrf2 was recorded. The concentration of unbound Keap1 was calculated using its standard curve, and the fraction of bound Keap1 was plotted against the concentration of the compounds. |
Dosage form | |
Applications | In a competitive surface plasmon resonance (SPR) assay, ML334 binds to Keap1 with a Kd of 1 μM. |
References: | |
| 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet