ML346
Based on 8 publication(s) in Google Scholar
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.
- Purity: 98.25%
- CAS No.: 100872-83-1
- Formula: C14H12N2O4
- Molecular Weight:272.26
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) ML346
More- ACS Nano. 2025 Feb 11;19(5):5659-5679. [Abstract]
- Cell Mol Gastroenterol Hepatol. 2026 May 12:101810. [Abstract]
- Clin Transl Med. 2023 Mar;13(3):e1229. [Abstract]
- Chem Biol Interact. 2023 Jan 5:369:110240. [Abstract]
- RSC Med Chem. 2021 Nov 1;13(2):138-149. [Abstract]
- J Biotechnol. 2025 Mar:399:9-18. [Abstract]
- bioRxiv. 2025 Nov 5.
- Res Sq. 2024 Nov 10.
Biological Activity
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HSP70 4.6 μM (EC50, HeLa cells) |
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 100872-83-1
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Appearance Solid
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Molecular Weight 272.26
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Formula C14H12N2O4
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Color Pink to red
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SMILES
O=C1NC(/C(C(N1)=O)=C/C=C/C2=CC=C(OC)C=C2)=O
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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 2 years -20°C 1 year
Publications (8)
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Journal Impact Factor
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Most Recent
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ACS Nano
Emerging of Ultrafine Membraneless Organelles as the Missing Piece of Nanostress: Mechanism of Biogenesis and Implications at Multilevels. [Abstract]2025 Feb 11;19(5):5659-5679. PMID: 39882824 -
Cell Mol Gastroenterol Hepatol
Kupffer Cell-Derived Exosomal S100A8/A9 Promotes Inflammasome-Dependent Pyroptotic Lung Injury in Acute Pancreatitis. [Abstract]2026 May 12:101810. PMID: 42128052 -
Clin Transl Med
Targeting lysosomal HSP70 induces acid sphingomyelinase-mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies. [Abstract]2023 Mar;13(3):e1229. PMID: 36959764 -
Chem Biol Interact
Low doses of fumonisin B1 exacerbate ochratoxin A-induced renal injury in mice and the protective roles of heat shock protein 70. [Abstract]2023 Jan 5:369:110240. PMID: 36397609 -
RSC Med Chem
Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella. [Abstract]2021 Nov 1;13(2):138-149. PMID: 35308030 -
J Biotechnol
2025 Mar:399:9-18. PMID: 39824361 -
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Solvent & Solubility
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)
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.
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.
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 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.
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.
Protocol
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (643 KB)
- English - EN (643 KB)
- Français - FR (643 KB)
- Deutsch - DE (643 KB)
- Norwegian - NO (643 KB)
- Español - ES (643 KB)
- Swedish - SV (643 KB)
- Italian - IT (643 KB)
- Korean - KR (643 KB)
- Portuguese - PT (643 KB)
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Handling Instructions (2659 KB)
References
[1]. Calamini B, et al. ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases.Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. 2012 Dec 17. [Content Brief]
[2]. Calamini B, et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol. 2011 Dec 25;8(2):185-96. [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, 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 |
ML346 Related Classifications
HY-18669 Related Classifications
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