GLPBio

ML-SI1

Catalog No.: GC19764Purity:>99.50%Synonyms: DMSO : 100 mg/mL (222.53 mM; Need ultrasonic)
ML-SI1 is a racemic mixture and an inhibitor of transient receptor potential cation channel (TRPML), with an IC50 value of 15μM for TRPML1.

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ML-SI1
1mgIn Stock
$145.00
1
5mgIn Stock
$333.00
1
10mgIn Stock
$551.00
1
25mgIn Stock
$1,045.00
1
50mgIn Stock
$1,615.00
1
100mgIn Stock
$2,375.00
1

Citations

2 publicationsPublications from researchers using this product

Description

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:
[1] Kim B, Jung J. Metabolomic approach to identify potential biomarkers in KRAS-Mutant pancreatic cancer cells[J]. Biomedicines, 2024, 12(4): 865.

Product Documents

Purity:>99.50%Appearance:A solid

Chemical Properties

Synonyms
DMSO : 100 mg/mL (222.53 mM; Need ultrasonic)
SMILES
O=C(N1C2=CC=C(C=C2C(C1C)CCN3CCOCC3)OC)C4=C(Cl)C(Cl)=CC=C4.[Mixture of diastereomers]
Molecular Formula
C₂₃H₂₆Cl₂N₂O₃
Molecular Weight
449.37
Solubility
DMSO : 100 mg/mL (222.53 mM)
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
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.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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