ML334 (Synonyms: LH601) |
カタログ番号GC38819
One-Click Copy Product Info
|
ML334は、細胞透過性の強力なNRF2活性化剤である。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1432500-66-7
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
ML334は、細胞透過性の強力なNRF2活性化剤である。これはKeap1-NRF2タンパク質間相互作用の阻害を通じて作用する。ML334は競合的表面プラズモン共鳴（SPR）アッセイにおいて、解離定数（Kd）1μMのKeap1に対する結合親和性を示した。さらに、ML334は蛍光偏光（FP）アッセイにおいてNrf2ペプチドと競合し、IC50が1.6μMを示した。
ML334（100μM、3時間）はHEK293細胞において核因子（erythroid-derived 2)-like 2(NRF2）の発現と核内移行を誘導する。一方、ML334処理は、HEK293細胞においてHO-1およびTRX1タンパク質の発現を誘導した。ML334誘導（50μM、48時間）のNrf2の過剰発現は、心臓線維芽細胞におけるパナックストリオールサポニン（PTS）の抗線維化効果を強化した。
[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.
細胞実験 [1]: | |
細胞株 | HEK293細胞 |
準備方法 | 細胞はML334を3時間処理された。 |
反応条件 | 100 μM; 3時間 |
アプリケーション | ML334はHEK293細胞において、核因子（エリスロイド由来2様因子：NRF2）の発現と核内移行を増強する。 |
競合SPRアッセイ [2]: | |
動物モデル | |
準備方法 | Nrf2のKeap1結合領域のビオチン化16merペプチドをCM5チップ表面（300RU）にストレプトアビジンで捕捉した。40nMのKeap1タンパク質のKelchドメインを含む溶液を、ML334とプレインキュベートし、固定化されたNrf2ペプチド表面上に注入した。アッセイは25℃、流速50μL/minで行い、会合時間1分、解離時間3分とした。センサーチップ表面を1M NaClで100μL/minの流速で1分間再生し、同じ流速のランニングバッファーで1分間の連続洗浄を2回行った。Nrf2に対するKeap1の結合シグナルを記録した。未結合のKeap1の濃度は標準曲線を用いて計算し、結合したKeap1の割合を化合物の濃度に対してプロットした。 |
投与形態 | |
アプリケーション | 競合表面プラズモン共鳴（SPR）アッセイにおいて、ML334はKeap1に1μMのKdで結合する。 |
参考文献: [1]: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. | |
| Cas No. | 1432500-66-7 | SDF | |
| 同義語 | LH601 | ||
| 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 | ||
| Formula | C26H26N2O5 | M.Wt | 446.5 |
| 溶解度 | DMSO: 44.65 mg/mL (100.00 mM); Ethanol: 44.65 mg/mL (100.00 mM) | Storage | Store at -20°C, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2396 mL | 11.1982 mL | 22.3964 mL |
| 5 mM | 447.9 μL | 2.2396 mL | 4.4793 mL |
| 10 mM | 224 μL | 1.1198 mL | 2.2396 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)