1. Cell Cycle/DNA Damage Metabolic Enzyme/Protease
  2. HSP
  3. ML346

ML346, a probe, has been extensively tested by the assay provider in several mechanism-of-action and protein folding assays.
ML346 (0-25μM; 24 hours) is not toxic to HeLa cells. ML346 increases the expression of Hsp70 mRNA by 2.4-fold. ML346 induces Hsp70, Hsp40, and Hsp27 expression.
ML346 activates transcription of the Hsp70 promoter.

ML346 is an activator of Hsp70 expression and HSF-1 activity, with an EC50 of 4.6 μM for Hsp70. ML346 restores protein folding in conformational disease models, without significant cytotoxicity or lack of specificity. ML346 induces specific increases in genes and protein effectors of the heat shock response (HSR), including chaperones such as Hsp70, Hsp40, and Hsp27.

For research use only. We do not sell to patients.

ML346 Chemical Structure

ML346 Chemical Structure

CAS No. : 100872-83-1

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 109 In-stock
Solution
10 mM * 1 mL in DMSO USD 109 In-stock
Solid
5 mg USD 99 In-stock
10 mg USD 154 In-stock
50 mg USD 385 In-stock
100 mg USD 605 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 3 publication(s) in Google Scholar

Top Publications Citing Use of Products

View All HSP Isoform Specific Products:

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

ML346 is an activator of Hsp70 expression and HSF-1 activity, with an EC50 of 4.6 μM for Hsp70. ML346 restores protein folding in conformational disease models, without significant cytotoxicity or lack of specificity. ML346 induces specific increases in genes and protein effectors of the heat shock response (HSR), including chaperones such as Hsp70, Hsp40, and Hsp27[1].

IC50 & Target[1]

HSP70

4.6 μM (EC50, HeLa cells)

In Vitro

ML346 is an activator of Hsp70, with an EC50 of 4600 nM in HeLa cells. ML346 (10 μM) restores proteostasis, restores CFTR-mediated iodide conductance, and enhances the correct folding of proteins expressed in two different cellular compartments[1]. ML346 (Compound F1) induces multiple responses and strongly induces Hsp70, the oxidative stress response genes (HO1 and GCLM), and a 2.5-fold upregulation of BiP in WT MEF cells. ML346 (0.5-25 μM) exhibits cytoprotective effects in cells after a 35 min severe heat shock, and also causes a two-fold protection from H2O2-induced apoptosis[2].

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

In Vivo

ML346 suppress the aggregation of polyQ35 in a C. elegans model, suggesting the probe has efficacy in modifying protein aggregation and associated toxicity[1].

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

Molecular Weight

272.26

Formula

C14H12N2O4

CAS No.
Appearance

Solid

Color

Pink to red

SMILES

O=C1NC(/C(C(N1)=O)=C/C=C/C2=CC=C(OC)C=C2)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 12.5 mg/mL (45.91 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 3.6730 mL 18.3648 mL 36.7296 mL
5 mM 0.7346 mL 3.6730 mL 7.3459 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
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% (20% SBE-β-CD in Saline)

    Solubility: ≥ 1.25 mg/mL (4.59 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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
Kinase Assay
[2]

In brief, HeLa cells are incubated with either DMSO (negative control), the positive controls MG132 (10 μM) and lactacystin (6 μM) or the PRs A1, A3 and ML346 (F1) for 3 and 6 hours and then harvested. Cells are lysed in homogenization buffer (50 mM Tris-HCl, pH7.5, 250 mM sucrose, 5 mM MgCl2, 2 mM ATP, 1 mM DTT, 0.5 mM EDTA, 0.025% digitonin) for 5 min on ice, and total protein concentration of whole cell extract is determined. 3 μg of whole cell extracts are combined with assay buffer (50 mM Tris-HCl, pH 7.5, 40 mM KCl, 5 mM MgCl2, 0.5 mM ATP, 1 mM DTT, 0.05 mg/mL BSA) in a black 96-well plate and the reaction is initiated by the addition of a 2× (200 μM) fluorogenic peptide substrate Suc-LLVY-AMC. Fluorescence is measured every 10 min using a Synergy H4 multi-mode microplate reader[2].

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

Cell Assay
[2]

HeLa cells are plated at a density of 10,000 cells per well in black 96-well plates in 100 μL of DMEM supplemented with 10% FBS and 1% Pen/Strep/Neo. Plates are incubated for 16 hours at 37°C, 5% CO2 and 95% relative humidity before compound addition. 1 μL of hit compounds (ML346) in DMSO or DMSO alone are added to the sample or control wells, respectively. Plates are then placed back in the incubator for 24 hours. After incubation, cells are washed 2× with 200 μL of PBS and 200 μL of a solution of 1 μg/mL of calcein AM is added to each well. Cells are then incubated for 45 min at 37°C, 5% CO2 before fluorescence measurement using an Analyst GT multimode reader. Percent cytotoxicity is expressed relative to wells containing cells treated with DMSO only (100%)[2].

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

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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.6730 mL 18.3648 mL 36.7296 mL 91.8240 mL
5 mM 0.7346 mL 3.6730 mL 7.3459 mL 18.3648 mL
10 mM 0.3673 mL 1.8365 mL 3.6730 mL 9.1824 mL
15 mM 0.2449 mL 1.2243 mL 2.4486 mL 6.1216 mL
20 mM 0.1836 mL 0.9182 mL 1.8365 mL 4.5912 mL
25 mM 0.1469 mL 0.7346 mL 1.4692 mL 3.6730 mL
30 mM 0.1224 mL 0.6122 mL 1.2243 mL 3.0608 mL
40 mM 0.0918 mL 0.4591 mL 0.9182 mL 2.2956 mL
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

ML346 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.

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

 

Salutation

Applicant Name *

 

Email Address *

Phone Number *

 

Organization Name *

Department *

 

Requested quantity *

Country or Region *

     

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
ML346
Cat. No.:
HY-18669
Quantity:
MCE Japan Authorized Agent: