| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
ML-SA5 targets the TRPML1 (MCOLN1) cation channel, which is primarily localized on late endosomes and lysosomes. Upon binding, the compound activates the channel, triggering lysosomal Ca2+ release. This Ca2+ signaling regulates lysosomal exocytosis, membrane trafficking, autophagy, and the activity of transcription factor EB (TFEB), which is a master regulator of lysosomal biogenesis. ML-SA5 is a more potent agonist than earlier compounds such as ML-SA1.
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| ln Vitro |
ML-SA5 (1-100 μM, 24 h) exhibits specificity in targeting cells and can cause a significant loss of M12 and MeWo cells while leaving normal melanocytes entirely intact. It also results in M12 cells losing their potential for the mitochondrial membrane [1].
ML-SA5 activates the entire endolysosomal TRPML1-mediated current (IML1) with an EC50 of 285 nM (or 333 nM in isolated vacuoles). At concentrations of 1-100 uM for 24 hours, the compound induces cell death in various cancer cell lines by triggering autophagic stasis, followed by apoptotic response and cell cycle arrest. ML-SA5 is reported to have minimal or no effect on normal cells, suggesting a degree of cancer cell selectivity. |
| ln Vivo |
ML-SA5 (ip, 2-5 mg/kg, daily, 2 weeks) reduced muscle necrosis in MDX mice by more than 70% and reduced central nucleated fibers, indicating that ML-SA5 can improve MDX mice via Muscle atrophy in vivo: Promotes myosin repair but has little effect in ML1 null mice. Furthermore, ML-SA5 decreases skeletal and cardiac injury in mdx mice by upregulating ML1 [2].
ML-SA5 (intraperitoneal injection, 2-5 mg/kg for 2 weeks) reduces muscle necrosis in MDX (dystrophic) mice by more than 70% and reduces central nucleated fibers. In a DSS-induced colitis mouse model, ML-SA5 (0.1 mg/kg, i.p.) significantly suppresses elevated IL-1beta protein levels in colonic tissues and serum, and these protective effects are abolished by co-administration of the TRPML1 antagonist ML-SI3 or in MCOLN1 knockout mice, confirming target engagement. |
| Enzyme Assay |
The TRPML1 channel activity is assessed using whole-endolysosomal patch-clamp electrophysiology. Isolated vacuoles enlarged by vacuolin-1 are used in patch-clamp recordings. ML-SA5 is applied to the intracellular (luminal) or extracellular side of the patch, and the resulting TRPML1-mediated currents (IML1) are recorded. The EC50 is calculated from the dose-response curve. Alternatively, calcium imaging using lysosome-targeted calcium indicators (e.g., GCaMP3 fused to a lysosomal membrane protein) can measure Ca2+ release upon ML-SA5 treatment.
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| Cell Assay |
Cellular activity is assessed in HeLa, cancer cell lines, or bone marrow-derived macrophages. Cells are treated with ML-SA5 at 0.05-10 uM for 1-24 hours. Autophagic flux is assessed by measuring LC3-II levels by Western blot, with or without lysosomal inhibitors (e.g., chloroquine). Lysosomal Ca2+ release is measured using lysosomal-targeted calcium sensors. Cancer cell viability is assessed by MTT or CellTiter-Glo assays after 24-72 hours of treatment. Apoptosis is detected by Annexin V/PI staining and caspase-3 cleavage.
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| Animal Protocol |
In a DSS-induced colitis model, female C57BL/6 mice are given 2.5-3% DSS in drinking water for 5-7 days. ML-SA5 is administered via intraperitoneal injection at doses ranging from 0.01-10 mg/kg daily. Disease activity index (body weight loss, stool consistency, bleeding) is monitored. Upon study termination, colon length is measured, and colonic tissues are collected for IL-1beta ELISA, Western blot, and histological analysis. In MDX mice (muscular dystrophy model), ML-SA5 is administered i.p. at 2-5 mg/kg for 2 weeks, and muscle necrosis and central nucleated fibers are assessed histologically.
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| ADME/Pharmacokinetics |
ML-SA5 is suitable for in vivo studies with an EC50 in the nanomolar range. It is typically administered via intraperitoneal injection at doses of 0.1-10 mg/kg. The compound shows good in vivo tolerability, with efficacy observed at 0.1 mg/kg in colitis models. In MDX mice, 2-5 mg/kg i.p. for 2 weeks reduces muscle necrosis without reported toxicity. Specific quantitative PK parameters (t1/2, Cmax, AUC) are not detailed, but the compound's in vivo activity confirms sufficient systemic exposure.
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| Toxicity/Toxicokinetics |
ML-SA5 has been tested in mouse models at doses of 0.1-10 mg/kg and is reported to be well tolerated. In MDX mice, 2-5 mg/kg i.p. for 2 weeks did not cause significant toxicity. The compound induces cancer cell death but has minimal or no effect on normal cells, suggesting a favorable therapeutic window. Toxicological data are limited to published research studies; full GLP toxicology studies have not been conducted as the compound is for research use only.
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| References | |
| Additional Infomation |
ML-SA5 is a research-grade chemical tool for studying TRPML1 channel function in lysosomal biology, autophagy, and cancer. TRPML1 is emerging as a therapeutic target for lysosomal storage disorders (e.g., mucolipidosis type IV), muscular dystrophy, and cancer, as TRPML1 agonists can enhance lysosomal function and clear pathological protein aggregates. ML-SA5 is a more potent and effective agonist than ML-SA1, making it a valuable tool for both basic and translational research. As of the latest updates, it has not been approved for clinical use.
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| Molecular Formula |
C19H24CLN3O4S2
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|---|---|
| Molecular Weight |
457.994561195374
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| Exact Mass |
457.089
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| CAS # |
2418670-70-7
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| PubChem CID |
154578372
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| Appearance |
White to light brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
600.4±65.0 °C at 760 mmHg
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| Flash Point |
316.9±34.3 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.623
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| LogP |
4.73
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
734
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YPPWKTIVYUTTEH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H24ClN3O4S2/c1-22(2)29(26,27)16-11-9-15(10-12-16)28(24,25)21-18-8-6-7-17(20)19(18)23-13-4-3-5-14-23/h6-12,21H,3-5,13-14H2,1-2H3
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| Chemical Name |
1-N-(3-chloro-2-piperidin-1-ylphenyl)-4-N,4-N-dimethylbenzene-1,4-disulfonamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~125 mg/mL (~272.93 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 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 20.8 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: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1835 mL | 10.9173 mL | 21.8345 mL | |
| 5 mM | 0.4367 mL | 2.1835 mL | 4.3669 mL | |
| 10 mM | 0.2183 mL | 1.0917 mL | 2.1835 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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