MDL-800

MDL-800 is a **selective allosteric activator of Sirtuin 6 (SIRT6)**, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase involved in key biological pathways such as DNA repair, metabolism, inflammation, aging, and tumor suppression[1][2][3][4][15][18]. MDL-800 preferentially enhances SIRT6 deacetylation activity (notably H3K9ac and H3K56ac) with an EC50 of approximately 10-11 μM and does not activate other SIRT family members or classical HDACs at relevant concentrations[4][10][15][18]. Preclinical studies show that MDL-800 suppresses proliferation of various cancer cell lines—including non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC)—through SIRT6-mediated deacetylation of H3 and cell-cycle arrest, and enhances the efficacy of EGFR tyrosine kinase inhibitors in resistant NSCLC[1][13]. MDL-800 also demonstrates efficacy in promoting DNA repair, improving genomic stability in aged cells and iPSCs, and has shown effects in wound healing, osteoarthritis, and neuroprotection via SIRT6 activation—proposed mechanisms include upregulation of NHEJ and BER DNA repair and inhibition of NF-κB inflammatory signaling[3][6][7][14]. It is used for research purposes and is not approved for clinical use.

Other names

Benzoic acid, 2-[[(5-bromo-4-fluoro-2-methylphenyl)amino]sulfonyl]-5-[[(3,5-dichlorophenyl)sulfonyl]amino]-, methyl estermethyl 2-(N-(5-bromo-4-fluoro-2-methylphenyl)sulfamoyl)-5-(3,5-dichlorophenylsulfonamido)benzoate