| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 15 μM (TRPML1)[1]
ML-SI1 targets the transient receptor potential mucolipin subfamily member 1 (TRPML1), a non-selective cation channel primarily localized to the membranes of late endosomes and lysosomes. It is a selective antagonist that shows a weak effect on the related TRPML2 channel, making it a specific tool for studying TRPML1 functions. |
|---|---|
| ln Vitro |
ML-SI1 is an indivisible racemic mixture of cis- and trans-isomers (55:45) in a brief synthetic sequence that, when activated with ML-SA1, exhibits inhibitory activity on hTRPML1 (and a negligible effect on TRPML2). Experiments using Fura-2 for single cell calcium imaging verified that the synthetic racemic ML-SI1 (10 μM) inhibits hTRPML1[1].
ML-SI1 inhibits the TRPML1 channel with an IC₅0 value of 15 microM. It acts as an antagonist, blocking the channel activated by the known agonist ML-SA1. This inhibition has been confirmed using single-cell calcium imaging experiments with Fura-2 dye. It has an IC50 of 15 microM for TRPML1. |
| ln Vivo |
Specific in vivo activity data for ML-SI1 is not available in the standard literature. As a research antagonist, its in vivo effect would typically be evaluated in animal models of diseases where lysosomal dysfunction is suspected, such as certain neurodegenerative disorders. Specific in vivo efficacy results are not reported.
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| Enzyme Assay |
Standard biochemical protocols for assessing TRPML1 activity involve whole-cell patch-clamp electrophysiology to directly measure the ion current flowing through the channel in the presence or absence of an inhibitor. Alternatively, fluorescent-based assays using the calcium-sensitive dye Fura-2 can be used to measure agonist-induced calcium influx in cells overexpressing the channel.
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| Cell Assay |
Typical cellular protocols for assessing the inhibitory activity of compounds like ML-SI1 involve loading cells (e.g., HEK293 cells overexpressing human TRPML1) with a calcium indicator dye such as Fura-2 or Fluo-4. Cells are pre-treated with ML-SI1 at various concentrations, and then the TRPML1-specific agonist ML-SA1 is added. The resulting change in intracellular calcium concentration is measured using a fluorescence plate reader or a fluorescence microscope.
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| Animal Protocol |
Standard procedures for testing TRPML1 antagonists in vivo involve administering the compound (e.g., by intraperitoneal injection) to disease model mice, such as those modeling lysosomal storage disorders or neurodegenerative diseases. After treatment, tissues are collected to assess lysosomal morphology and function by electron microscopy or Western blot for biomarkers of lysosomal stress.
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| ADME/Pharmacokinetics |
ML-SI1 is a small molecule with a molecular weight of 449.37. For in vitro use, it is soluble in DMSO (typically used for stock solutions). For in vivo application, it can be formulated using co-solvents like a 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline mixture.
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| Toxicity/Toxicokinetics |
No specific toxicological data for ML-SI1 is available in standard literature. As a TRPML1 antagonist, its toxicity profile is expected to be related to the disruption of normal lysosomal functions. However, for a research compound, typical cell viability assays (e.g., MTT) would be required to determine its safety margin, but such data are not standardly published for this reagent.
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| References | |
| Additional Infomation |
ML-SI1 is a research-grade chemical probe used to elucidate the roles of TRPML1 in cellular processes such as lysosomal biogenesis, autophagy, membrane trafficking, and metal ion homeostasis. It is strictly for laboratory research use and is not intended for diagnostic or therapeutic purposes. It has not been approved by the FDA or any other regulatory agency for human use.
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| Molecular Formula |
C23H26CL2N2O3
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|---|---|
| Molecular Weight |
449.37
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| Appearance |
Off-white to yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~222.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2253 mL | 11.1267 mL | 22.2534 mL | |
| 5 mM | 0.4451 mL | 2.2253 mL | 4.4507 mL | |
| 10 mM | 0.2225 mL | 1.1127 mL | 2.2253 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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