ML-SI1 (Synonyms: DMSO : 100 mg/mL (222.53 mM; Need ultrasonic)) |
カタログ番号GC19764
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ML-SI1はラセミ混合物であり、一過性受容体電位カチオンチャネル（TRPML）の阻害剤であり、TRPML1に対するIC50値は15μMである。
Products are for research use only. Not for human use. We do not sell to patients.
Sample solution is provided at 25 µL, 10mM.
ML-SI1はラセミ混合物であり、一過性受容体電位カチオンチャネル（TRPML）の阻害剤であり、TRPML1に対するIC50値は15μMである[1, 2]。TRPML1はリソソームカチオンチャネルであり、リソソーム生合成、エンドリソソーム輸送（神経樹状突起における輸送を含む）、そしてオートファジーに関与している[3]。ML-SI1とML-SI3は今の時点で、発表された2つだけのTRPML阻害剤である[4]。
体外で、ML-SI1 (0-100μM)でPANC1細胞を48時間処理した結果、細胞の生存率を著しく減らし、代謝プロファイルにおける著しい変化を誘発した[5]。ML-SI1 (20μM)で海馬体ニューロンを2時間処理した結果、LAMTOR1ノックダウンによるリソソーム局在化の変化を遮断した[6]。ML-SI1 (1.25μM)でIPEC-J2細胞を24時間処理した結果、AFB1によるROSとCa2+のレベルを著しく減らし、細胞アポトーシスとオートファジーを著しく減らした[7]。
References:
[1] Reeks J, Mahajan P, Clark M, et al. High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1[J]. Structure, 2025.
[2] Leser C, Keller M, Gerndt S, et al. Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3[J]. European journal of medicinal chemistry, 2021, 210: 112966.
[3] Wang W, Zhang X, Gao Q, et al. TRPML1: an ion channel in the lysosome[J]. Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume I, 2014: 631-645.
[4] Kriegler K, Leser C, Mayer P, et al. Effective chiral pool synthesis of both enantiomers of the TRPML inhibitor trans‐ML‐SI3[J]. Archiv der Pharmazie, 2022, 355(2): 2100362.
[5] Kim B, Jung J. Metabolomic approach to identify potential biomarkers in KRAS-Mutant pancreatic cancer cells[J]. Biomedicines, 2024, 12(4): 865.
[6] Sun J, Lin W, Hao X, et al. LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition[J]. Frontiers in Cellular Neuroscience, 2024, 18: 1495546.
[7] Cheng X, Liang J, Wu D, et al. Blunting ROS/TRPML1 pathway protects AFB1-induced porcine intestinal epithelial cells apoptosis by restoring impaired autophagic flux[J]. Ecotoxicology and Environmental Safety, 2023, 257: 114942.
| 細胞実験[1]: | |
細胞株 | PANC1細胞 |
準備方法 | 細胞をML-SI1で48時間処理し、そして、暗処、37℃で、2mg/mL MTT溶液で3時間インキュベートした。その後、DMSOを添加し、生細胞で産生されたホルマザン結晶を溶解した。マイクロプレートリーダーで、540nmで吸光度を測定した。 |
反応条件 | 0-100μM；48時間 |
アプリケーション | ML-SI1を使ってのTRPML1の薬理学的阻害は、PANC1細胞の生存率を著しく減らした。 |
References: | |
| Cas No. | SDF | ||
| 同義語 | DMSO : 100 mg/mL (222.53 mM; Need ultrasonic) | ||
| Canonical SMILES | O=C(N1C2=CC=C(C=C2C(C1C)CCN3CCOCC3)OC)C4=C(Cl)C(Cl)=CC=C4.[Mixture of diastereomers] | ||
| Formula | C₂₃H₂₆Cl₂N₂O₃ | M.Wt | 449.37 |
| 溶解度 | DMSO : 100 mg/mL (222.53 mM) | Storage | Store at -20°C |
| 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2253 mL | 11.1267 mL | 22.2534 mL |
| 5 mM | 445.1 μL | 2.2253 mL | 4.4507 mL |
| 10 mM | 222.5 μL | 1.1127 mL | 2.2253 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)