Allosteric activator of SIRT6 (EC50 = 10.3 µM).1 It specifically activates the deacetylase (H3K9ac and H3K56ac) activity of SIRT6 - inactive against SIRT1,3,4 and HDACs 1-11 with 10x less activity against SIRT2,5,7. It inhibited the growth of human hepatocarcinoma cells (HCC) via the tumor suppressor deacetylase (H3K9ac and H3K56ac) via cell-cycle arrest and showed efficacy in a xenograft model of HCC. MDL-800 improved the genetic stability of old-murine-derived iPSCs via activation of NHEJ and BER DNA repair pathways suggesting promise in treating age-related diseases via iPSC-based therapies.2 MDL-800 inhibited the proliferation of 12 non-small cell lung carcinoma cell lines with IC50 values of 21.5 to 34.5 µM.3 It also enhanced the effects of EGFR kinase inhibitors in Osimertinib-resistant HCC827 and PC9 cells as well as in patient-derived primary tumor cells.3
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