2. Anti-infection Membrane Transporter/Ion Channel Neuronal Signaling
  3. Parasite TRP Channel
  4. ML-SI3

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.

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ML-SI3 Chemical Structure

ML-SI3 Chemical Structure

CAS No. : 891016-02-7

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

Other Forms of ML-SI3:

ML-SI3 Related Antibodies

Top Publications Citing Use of Products

1 Publications Citing Use of MCE ML-SI3

View All Parasite Isoform Specific Products:

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Amebae Coccidia Leishmania Mite Plasmodium Toxoplasma Trypanosoma Schistosome

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TRPC TRPM TRPV TRPA TRPML

  • Biological Activity

  • Purity & Documentation

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Description

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[1][2].

IC50 & Target[1]

Schistosome

 

TRPML1

4.7 μM (IC50)

TRPML2

1.7 μM (IC50)

TRPML3

12.5 μM (IC50)

In Vitro

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.

ML-SI3 Related Antibodies
In Vivo

ML-SI3 (1.5 mg/kg, i.p., four times) attenuates I/R injury in mouse cardiomyocytes[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Myocardial Ischemia/reperfusion (I/R) injury mice[5]
Dosage: 1.5 mg/kg
Administration: Intraperitoneal injection (i.p.), four times before and during the in vivo I/R (ischemia 30 min and reperfusion 1 day)
Result: Restored the blocked autophagic fux in the cardiomyocytes subjected to I/R.
Molecular Weight

429.58

Formula

C23H31N3O3S
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=S(C1=CC=CC=C1)(NC2C(N3CCN(C4=CC=CC=C4OC)CC3)CCCC2)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.3279 mL 11.6393 mL 23.2786 mL
5 mM 0.4656 mL 2.3279 mL 4.6557 mL
View the 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.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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
References

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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ML-SI3 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ML-SI3891016-02-7ML-SI3 (cis/trans mix)ParasiteTRP ChannelTransient receptor potential channelsCa2+SchistosomesNRVMI/R injuryautophagic fuxInhibitorinhibitorinhibit

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