MDL 800 |
Katalog-Nr.GC52188
One-Click Copy Product Info
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MDL 800 is a selective allosteric activator of Sirtuin 6 (SIRT6) with EC50 value of 10.3μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2275619-53-7
Sample solution is provided at 25 µL, 10mM.
MDL 800 is a selective allosteric activator of Sirtuin 6 (SIRT6) with EC50 value of 10.3μM[1]. SIRT6, widely expressed in almost all mammalian organs, is involved in many biological processes, such as DNA repair, glucose/lipid metabolism, inflammation, aging and tumor suppression[2 - 4].
In vitro, treatment of NSCLC cells with MDL 800(10–50μM, 48h) increased SIRT6 deacetylase activity, induced deacetylation of histone H3 and inhibited cell proliferation in a dose-dependent manner[5]. MDL 800 (0.1-5µM) inhibits TNF-α release induced by oxygen and glucose deprivation (OGD) in primary mouse microglia[6].
In vivo,intraperitoneal injection of MDL 800(50, 100, and 150mg/kg/day) for 2 weeks suppressed the growth of Bel7405 xenografts and decreased tumor weight and size in a dose-dependent manner in mouse model with Bel7405 xenograft[1]. In mice with a full thickness cutaneous wound model, itraperitoneal injection of MDL 800(5, 25mg/kg/day) for 7 days attenuated the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds. Furthermore, MDL 800 significantly downregulated expression levels of TNF-α and IL-6 in the dorsal skin tissue of mice[7].
References:
[1] Huang, Z., Zhao, J., Deng, W., Chen, Y., Shang, J., Song, K., Zhang, L., Wang, C., Lu, S., Yang, X., He, B., Min, J., Hu, H., Tan, M., Xu, J., Zhang, Q., Zhong, J., Sun, X., Mao, Z., Lin, H., … Zhang, J. (2018). Identification of a cellularly active SIRT6 allosteric activator. Nature chemical biology, 14(12), 1118–1126.
[2] Kugel, S., & Mostoslavsky, R. (2014). Chromatin and beyond: the multitasking roles for SIRT6. Trends in biochemical sciences, 39(2), 72–81.
[3] Tasselli, L., Zheng, W., & Chua, K. F. (2017). SIRT6: Novel Mechanisms and Links to Aging and Disease. Trends in endocrinology and metabolism: TEM, 28(3), 168–185.
[4] Van Meter M, Gorbunova V, Seluanov A. SIRT6: a promising target for cancer prevention and therapy. Advances in Experimental Medicine and Biology, 2014, 818: 181-196.
[5] Shang, J. L., Ning, S. B., Chen, Y. Y., Chen, T. X., & Zhang, J. (2021). MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. Acta pharmacologica Sinica, 42(1), 120–131.
[6] He, T., Shang, J., Gao, C., Guan, X., Chen, Y., Zhu, L., Zhang, L., Zhang, C., Zhang, J., & Pang, T. (2021). A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis. Acta pharmaceutica Sinica. B, 11(3), 708–726.
[7] Jiang, X., Yao, Z., Wang, K., Lou, L., Xue, K., Chen, J., Zhang, G., Zhang, Y., Du, J., Lin, C., & Xiao, J. (2022). MDL-800, the SIRT6 Activator, Suppresses Inflammation via the NF-κB Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice. Oxidative medicine and cellular longevity, 2022, 1619651.
| Cell experiment [1]: | |
Cell lines | NSCLC cells |
Preparation Method | NSCLC cells were seeded (n = 3 wells/group) in 96-well plates at a density of 5 × 103 cells per well. After attaching overnight, NSCLC cells were treated with MDL 800 at various concentrations(10–50μM). Cells treated with DMSO were used as positive controls. After 48h of treatment, CCK-8 (10μL/well) was added and incubated for 1h at 37 °C. To measure the number of viable cells, the absorbance of each well was detected at 450nm using a microplate reader (Synergy H4 Hybrid Reader, BioTek). The relative viability of each group is presented as the percentage change relative to the positive control group. |
Reaction Conditions | 10–50μM; 48h |
Applications | MDL 800 increased SIRT6 deacetylase activity ,induced deacetylation of histone H3 and inhibited cell proliferation in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | male Balb/c mice |
Preparation Method | Thirty mice were randomly divided into three groups of ten: the saline control group, the low MDL 800 concentration group (5mg/kg), and the high MDL 800 concentration group (25mg/kg). Prior to mouse injection, sterile saline containing 5% polyethylene glycol 400 (PED- 400) was placed in a 37° C incubator for standby use. The MDL 800 mother liquor was then diluted into different concentrations and shaken to obtain a uniform solution. The mice were anesthetized with 1% pentobarbital sodium, and their dorsal fur was shaved and sterilized with 75% ethanol. A biopsy punch was used to make two full-thickness excision wounds (8mm in diameter) on both sides. After surgery, mice were injected daily with MDL 800 or vehicle (containing 5% PED-400) around the wound bed for 7 days. The changes in the wounds were then observed and documented. Photographs of the wounds were taken on days 0, 3, 6, 9, and 18 postoperation and analyzed using ImageJ. On days 9 and 18, mice were sacrificed after anesthesia. After that, the wound tissues were excised and fixed, paraffin-embedded, and sectioned (5μm thick). |
Dosage form | 5,25mg/kg/day for 7 days; i.p. |
Applications | MDL 800 attenuated the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds. Furthermore, MDL 800 significantly downregulated expression levels of TNF-α and IL-6 in the dorsal skin tissue of mice. |
References: | |
| Cas No. | 2275619-53-7 | SDF | |
| Canonical SMILES | CC1=C(NS(C2=C(C(OC)=O)C=C(NS(C3=CC(Cl)=CC(Cl)=C3)(=O)=O)C=C2)(=O)=O)C=C(Br)C(F)=C1 | ||
| Formula | C21H16BrCl2FN2O6S2 | M.Wt | 626.3 |
| Löslichkeit | DMF: 10 ma/ml; 100mg/ml in DMSO | 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 | 1.5967 mL | 7.9834 mL | 15.9668 mL |
| 5 mM | 319.3 μL | 1.5967 mL | 3.1934 mL |
| 10 mM | 159.7 μL | 798.3 μL | 1.5967 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)