Citations
2 publicationsPublications from researchers using this productDescription
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.
Protocol
| Cell experiment [1]: | |
|
Cell lines |
PANC1 cells |
|
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. |
|
Reaction Conditions |
0-100μM; 48h |
|
Applications |
Pharmacological inhibition of TRPML1 using ML-SI1 significantly decreased PANC1 cell viability. |
|
References: |
|
Product Documents
Chemical Properties
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility
Reviews
Review for ML-SI1
- 5 Star100%
- 4 Star0%
- 3 Star0%
- 2 Star0%
- 1 Star0%
