ML-SI1是一种外消旋混合物，是瞬时受体电位阳离子通道（TRPML）的抑制剂，对TRPML1的IC50值为15μM。
Sample solution is provided at 25 µL, 10mM.
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ML-SI1 is a racemic mixture and an inhibitor of transient receptor potential cation channel (TRPML), with an IC50 value of 15μM for TRPML1[1, 2]. TRPML1 is a lysosomal cation channel involved in lysosomal biogenesis, endolysosomal trafficking (including trafficking in neuronal dendrites), and autophagy[3]. ML-SI1 and ML-SI3 are currently the only two published TRPML inhibitors[4].
In vitro, treatment of PANC1 cells with ML-SI1 (0-100μM) for 48h significantly reduced cell viability and induced significant changes in the metabolic profile[5]. Treatment of hippocampal neurons with ML-SI1 (20μM) for 2h blocked the lysosomal localization changes induced by LAMTOR1 knockdown[6]. Treatment of IPEC-J2 cells with ML-SI1 (1.25μM) for 24h significantly reduced ROS and Ca2+ levels induced by AFB1, and significantly decreased cell apoptosis and autophagy[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.
ML-SI1是一种外消旋混合物，是瞬时受体电位阳离子通道（TRPML）的抑制剂，对TRPML1的IC50值为15μM[1, 2]。TRPML1是一种溶酶体阳离子通道，与溶酶体生物合成、内体/溶酶体运输（包括神经元树突中的运输）以及自噬有关[3]。ML-SI1和ML-SI3是目前仅发表的两种TRPML抑制剂[4]。
在体外，ML-SI1（0-100μM）处理PANC1细胞48h，显著降低了细胞的活力，诱导了代谢物谱的明显变化[5]。ML-SI1（20μM）处理海马体神经元2h，阻断了LAMTOR1敲低引起的溶酶体定位变化[6]。ML-SI1（1.25μM）处理IPEC-J2 细胞24h，显著降低了AFB1诱导的细胞中的ROS和Ca2+水平，显著降低了细胞凋亡和自噬[7]。
| Cell experiment [1]: | |
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Cell lines |
PANC1 cells |
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Preparation Method |
Cells were treated with ML-SI1 for 48h, and then incubated with 2mg/mL MTT solution at 37°C in the dark for 3h. After incubation, DMSO was added to dissolve the formazan crystals produced by the living cells. Absorbance was then measured at 540nm using a microplate reader. |
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Reaction Conditions |
0-100μM; 48h |
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Applications |
Pharmacological inhibition of TRPML1 using ML-SI1 significantly decreased PANC1 cell viability. |
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References: |
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| Cas No. | SDF | ||
| Canonical SMILES | O=C(N1C2=CC=C(C=C2C(C1C)CCN3CCOCC3)OC)C4=C(Cl)C(Cl)=CC=C4.[Mixture of diastereomers] | ||
| 分子式 | C₂₃H₂₆Cl₂N₂O₃ | 分子量 | 449.37 |
| 溶解度 | DMSO : 100 mg/mL (222.53 mM) | 储存条件 | Store at -20°C |
| 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 | 2.2253 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 |
| 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
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- Purity: >99.50% Appearance: A solid
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