ML-SI3
Based on 8 publication(s) in Google Scholar
ML-SI3 is a mixture of cis/trans ML-SI3 (HY-139426A), which is a TRPML1/2 channel inhibitor with IC50s of 4.7 μM and 1.7 μM, respectively. ML-SI3 also inhibits lysosomal calcium efflux and blocks downstream TRPML1-mediated autophagy. The cis/trans ML-SI3 (HY-139426A) components of ML-SI3 are TRPML2 activators with EC50s of 3.3 μM and 9.4 μM, respectively.
For research use only. We do not sell to patients.
- Purity: 99.91%
- CAS No.: 891016-02-7
- Formula: C23H31N3O3S
- Molecular Weight:429.58
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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HY-L176
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HY-L181
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HY-L001V
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HY-L001
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High-Throughput Bioactive Compound Library
HY-L205
Publications Citing Use of MedChemExpress (MCE) ML-SI3
More- Nat Cell Biol. 2024 Aug;26(8):1247-1260. [Abstract]
- Adv Sci (Weinh). 2025 Sep 25:e12407. [Abstract]
- J Immunother Cancer. 2025 Oct 5;13(10):e012182. [Abstract]
- Cell Death Dis. 2025 Dec 23. [Abstract]
- Cell Mol Bioeng. 2025 Jan 21;18(1):39-52. [Abstract]
- FASEB J. 2026 Jan 15;40(1):e71421. [Abstract]
- Cell Signal. 2025 Jan 3:111583. [Abstract]
- bioRxiv. 2025 March 19.
Customer Validation & Images
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Cell Imaging/Staining
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Cell Imaging/Staining
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WB
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Cell Imaging/Staining
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Flow Cytometry
All Parasite Isoforms
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Biological Activity
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Schistosome |
TRPML1 4.7 μM (IC50) |
TRPML2 1.7 μM (IC50) |
TRPML3 12.5 μM (IC50) |
ML-SI3 (10 μM) inhibits ML-SA1-evoked Ca2+ signals in HeLa cells[3].
ML-SI3 (25-75 μM, 24h) disrupts tegumental integrity of adult schistosomes[4].
ML-SI3 (10 μM) blocks Rapamycin (HY-10219)-evoked ITRPML1 in mimic of lysosomal lumen[5].
ML-SI3 (3 μM, 6 h) abolishes the increase in both LC3II and p62 levels induced by hypoxia/reoxygenation (H/R) (4 h H/2 h R) in neonatal rat ventricular myocytes (NRVM)[6].
Table: Activation and inhibition of the three subtypes of TRPML by Others ML-SI3-type compounds[2]
| Product_Names | Catalog_No | EC50 for activation [μM] | IC50 for inhibition [μM] | ||||
| TRPML1 | TRPML2 | TRPML3 | TRPML1 | TRPML2 | TRPML3 | ||
| (rel)-ML-SI3 | HY-139426A | - | 3.3±1.5 | - | 3.1±1.5 | - | 28.5±15.9 |
| (cis)-ML-SI3 | / | - | 9.4±2.7 | 29.0±4.1 | 18.5±1.9 | - | - |
| (1S,2S)-ML-SI3 | HY-134819 | - | 2.7±1.4 | 10.8±0.5 | 5.9±1.7 | - | - |
| (1R,2R)-ML-SI3 | HY-134819A | - | - | - | 1.6±0.7 | 2.3±1.1 | 12.5±7.6 |
| Mean values ± SD of at least three independent experiments are shown. -: no effect. | |||||||
| ML-SI3 | HY-139426 | The mixtrue of (rel)-ML-SI3 and (cis)-ML-SI3 | |||||
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Myocardial Ischemia/reperfusion (I/R) injury mice[5]
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Dosage:1.5 mg/kg
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Administration:Intraperitoneal injection (i.p.), four times before and during the in vivo I/R (ischemia 30 min and reperfusion 1 day)
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Result:Restored the blocked autophagic fux in the cardiomyocytes subjected to I/R.
Chemical Information
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CAS No. 891016-02-7
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Appearance Solid
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Molecular Weight 429.58
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Formula C23H31N3O3S
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Color White to off-white
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SMILES
O=S(C1=CC=CC=C1)(NC2C(N3CCN(C4=CC=CC=C4OC)CC3)CCCC2)=O
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Synonyms
ML-SI3 (cis/trans mix)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (8)
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Journal Impact Factor
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Most Recent
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Nat Cell Biol
2024 Aug;26(8):1247-1260. PMID: 38997458 -
Adv Sci (Weinh)
Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation. [Abstract]2025 Sep 25:e12407. PMID: 40995693
ML-SI3 purchased from MedChemExpress. Usage Cited in: Adv Sci (Weinh). 2025 Sep 25:e12407. [Abstract]
Under SD condition, ML-SI3 (10 μM) reversed the significant increases or decreases in intracellular calcium concentration, lysosome number, or anterograde transport distance caused by persistent overexpression or silencing of PITX2.
ML-SI3 purchased from MedChemExpress. Usage Cited in: Adv Sci (Weinh). 2025 Sep 25:e12407. [Abstract]
Representative Lyso-Tracker Red staining images showed the number and anterograde transport distance of lysosomes in AGS and HGC-27 cells stably transfected with mock, PITX2, sh-Scb, sh-PITX2 #1, or sh-PITX2 #2 under SD conditions and those treated with ML-SI3 (10 μM).
ML-SI3 purchased from MedChemExpress. Usage Cited in: Adv Sci (Weinh). 2025 Sep 25:e12407. [Abstract]
Western blot assay indicated the levels of PITX2, LC3, and SQSTM1 in AGS and HGC-27 cells stably transfected with mock, PITX2, sh-Scb, or sh-PITX2 #1 under SD conditions, and those treated with ML-SI3 (10 μM).
ML-SI3 purchased from MedChemExpress. Usage Cited in: Adv Sci (Weinh). 2025 Sep 25:e12407. [Abstract]
Representative images and quantification of autophagic flux reporters RFP- and GFP-LC3 (arrowheads) in AGS and HGC-27 cells stably transfected with empty vector (mock), PITX2, scramble shRNA (sh-Scb), or sh-PITX2 #1 under SD condition, and those treated with ML-SI3 (10 μM) were presented.
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J Immunother Cancer
Macrophage NLRP3 activation and IL-1β release drive osimertinib-induced antitumor immunity. [Abstract]2025 Oct 5;13(10):e012182. PMID: 41052880
ML-SI3 purchased from MedChemExpress. Usage Cited in: J Immunother Cancer. 2025 Oct 5;13(10):e012182. [Abstract]
Flow cytometry analysis of Fluo-4 AM (5 μM) staining in BMDM cells after osimertinib stimulation with or without ML-SI3 (5 μM) pretreatment. ML-SI3 inhibited Osimertinib-induced Ca2+ accumulation.
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Cell Death Dis
Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue. [Abstract]2025 Dec 23. PMID: 41436477 -
Cell Mol Bioeng
Hyperosmotic Stress Promotes the Nuclear Translocation of TFEB in Tubular Epithelial Cells Depending on Intracellular Ca2+ Signals via TRPML Channels. [Abstract]2025 Jan 21;18(1):39-52. PMID: 39949488 -
FASEB J
TRPML1 in Cisplatin-Induced Acute Kidney Injury: A New Target for Renal Tubular Epithelial Protection by Regulating Lysosomal Calcium Homeostasis. [Abstract]2026 Jan 15;40(1):e71421. PMID: 41499332 -
Cell Signal
HDAC inhibitor enhances ferroptosis susceptibility of AML cells by stimulating iron metabolism. [Abstract]2025 Jan 3:111583. PMID: 39756501 -
Solvent & Solubility
DMSO : 50 mg/mL (116.39 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (282 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Rühl P, et al. Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors. Sci Rep. 2021 Apr 15;11(1):8313. [Content Brief]
[2]. Leser C, et al. Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3. Eur J Med Chem. 2021 Jan 15;210:112966. [Content Brief]
[3]. Kilpatrick BS, et al. Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx. J Cell Sci. 2016 Oct 15;129(20):3859-3867. [Content Brief]
[4]. Bais S, et al. Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity. Biochimie. 2022 Mar;194:108-117. [Content Brief]
[5]. Zhang X, et al. Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR. PLoS Biol. 2019 May 21;17(5):e3000252. [Content Brief]
[6]. Xing Y, et al. Blunting TRPML1 channels protects myocardial ischemia/reperfusion injury by restoring impaired cardiomyocyte autophagy. Basic Res Cardiol. 2022 Apr 7;117(1):20. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3279 mL | 11.6393 mL | 23.2786 mL | 58.1964 mL |
| 5 mM | 0.4656 mL | 2.3279 mL | 4.6557 mL | 11.6393 mL | |
| 10 mM | 0.2328 mL | 1.1639 mL | 2.3279 mL | 5.8196 mL | |
| 15 mM | 0.1552 mL | 0.7760 mL | 1.5519 mL | 3.8798 mL | |
| 20 mM | 0.1164 mL | 0.5820 mL | 1.1639 mL | 2.9098 mL | |
| 25 mM | 0.0931 mL | 0.4656 mL | 0.9311 mL | 2.3279 mL | |
| 30 mM | 0.0776 mL | 0.3880 mL | 0.7760 mL | 1.9399 mL | |
| 40 mM | 0.0582 mL | 0.2910 mL | 0.5820 mL | 1.4549 mL | |
| 50 mM | 0.0466 mL | 0.2328 mL | 0.4656 mL | 1.1639 mL | |
| 60 mM | 0.0388 mL | 0.1940 mL | 0.3880 mL | 0.9699 mL | |
| 80 mM | 0.0291 mL | 0.1455 mL | 0.2910 mL | 0.7275 mL | |
| 100 mM | 0.0233 mL | 0.1164 mL | 0.2328 mL | 0.5820 mL |
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