ML-346 |
Catalog No.GC18170
One-Click Copy Product Info
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ML-346 es un activador de la expresión de Hsp70 y de la actividad de HSF-1, con una EC50 de 4,6 μM para Hsp70. ML-346 restaura el plegamiento de proteínas en modelos de enfermedades conformacionales, sin citotoxicidad significativa o falta de especificidad. ML-346 induce aumentos específicos en genes y proteínas efectoras de la respuesta al choque térmico (HSR), incluidas chaperonas como Hsp70, Hsp40 y Hsp27.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 100872-83-1
Sample solution is provided at 25 µL, 10mM.
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ML-346 is an activator of the heat shock response that induces the expression of the heat shock protein HSP70, with an EC50 value of 4.6µM[1]. ML-346 molecule covalently modified the cysteine (Cys) at position 208 of the active site of the housekeeping sorting enzyme A (SrtA) of Staphylococcus aureus, significantly reducing the virulence phenotype of Staphylococcus aureus[2]. ML-346 has been widely used in transplantation tumor models to promote tumor cell apoptosis and reduce tumor growth[3].
In vitro, ML-346 treatment (10µM) for 24 hours significantly inhibited the viability of MDA-MB-435 cells and reduced the activities of CDK7 and CDK9[4]. Treatment with 10µM ML-346 for 24 hours significantly inhibited the LC3 I/II conversion in A549 cells, and promoted the accumulation of p62 as well as a significant increase in the phosphorylation level of mTOR at the Ser2448 site[5]. 15µM of ML-346 pretreatment for 1 hour significantly inhibited the accumulation of sphingomyelin induced by V8 in Jurkat cells and the co-localization with Lysotracker Red[6]. 10µM of ML-346 pretreatment for 4 hours alleviated the mitochondrial damage and cell apoptosis induced by the combined action of Fumonisin B1 (FB1) and ochratoxin A (OTA) in pK-15 cells[7].
References:
[1] Calamini B, Silva M C, Madoux F, et al. ML346: a novel modulator of proteostasis for protein conformational diseases[M]//Probe Reports from the NIH Molecular Libraries Program [Internet]. National Center for Biotechnology Information (US), 2013.
[2] Guan X N, Zhang T, Yang T, et al. Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella[J]. RSC Medicinal Chemistry, 2022, 13(2): 138-149.
[3] Chen W, Wang Z, Ji J, et al. The regulatory mechanism of HSP70 in endoplasmic reticulum stress in pepsin-treated laryngeal epithelium cells and laryngeal cancer cells[J]. Aging (Albany NY), 2022, 14(20): 8486.
[4] Chiang S K, Chang W C, Chen S E, et al. CDK7/CDK9 mediates transcriptional activation to prime paraptosis in cancer cells[J]. Cell & Bioscience, 2024, 14(1): 78.
[5] Alhasan B, Gladova Y A, Sverchinsky D V, et al. Hsp70 negatively regulates autophagy via governing AMPK activation, and dual Hsp70-autophagy inhibition induces synergetic cell death in NSCLC Cells[J]. International Journal of Molecular Sciences, 2024, 25(16): 9090.
[6] Qing Y, Guo Y, Zhao Q, et al. Targeting lysosomal HSP70 induces acid sphingomyelinase‐mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies[J]. Clinical and translational medicine, 2023, 13(3): e1229.
[7] Li H, He W, Yue D, et al. Low doses of fumonisin B1 exacerbate ochratoxin A-induced renal injury in mice and the protective roles of heat shock protein 70[J]. Chemico-Biological Interactions, 2023, 369: 110240.
| Cell experiment [1]: | |
Cell lines | MDA-MB-435 cells |
Preparation Method | MDA-MB-435 cells were cultured in DMEM/F12 medium supplemented with 10% fetal bovine serum, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C with 5% CO2 and 95% saturated atmospheric humidity. Cells were seeded into 96-well microplates at a density of 5×103 cells/ml for 24h. Various concentrations of ML-346 (0, 2.5, 5, and 10µM) were added to each well. After 24h of incubation, cell viability was analyzed. |
Reaction Conditions | 0, 2.5, 5, and 10µM; 24h |
Applications | ML-346 treatment significantly inhibited the cell viability of MDA-MB-435 cells in a dose-dependent manner. |
References: | |
| Cas No. | 100872-83-1 | SDF | |
| Chemical Name | 5-[3-(4-methoxyphenyl)-2-propen-1-ylidene]-2,4,6(1H,3H,5H)-pyrimidinetrione | ||
| Canonical SMILES | O=C1NC(/C(C(N1)=O)=C/C=C/C2=CC=C(OC)C=C2)=O | ||
| Formula | C14H12N2O4 | M.Wt | 272.3 |
| Solubility | 0.5mg/mL in ethanol, 30mg/mL in DMSO, or in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6724 mL | 18.3621 mL | 36.7242 mL |
| 5 mM | 734.5 μL | 3.6724 mL | 7.3448 mL |
| 10 mM | 367.2 μL | 1.8362 mL | 3.6724 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 21 reference(s) in Google Scholar.)