MDL 800

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 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:
[1]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.
[2]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-?B Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice. Oxidative medicine and cellular longevity, 2022, 1619651.