MDL-811 (MDL811) is a potent, selective and allosteric SIRT6 activator with EC50 of 5.7 uM (activated SIRT6 deacetylation), two-fold greater activity than MDL-800 (EC50=12.3 uM, Cat# 35760).
MDL-811 shows little effect on other histone deacetylase (HDAC) enzymes.
MDL-811 shows significantly enhanced bioavailability (F%, 92.96%) compared with MDL-800 (71.33%).
MDL-811 significantly enhances the deacetylation of SIRT6 (H3K9Ac, H3K18Ac, and H3K56Ac) in natural nucleosomes and HEK293T cells in a dose-dependent manner.
MDL-811 exhibits broad antiproliferative effects on CRC cells (IC50=4.7-61 uM), binds and stabilize SIRT6 in CRC cells, reduces histone H3 acetylation through the activation of SIRT6 deacetylase activity.
MDL-811 (30 mg/kg, i.p.) exhibits robust anti-tumor efficacy in CRC CDX and PDX models, inhibits tumorigenesis in the APCmin/+ model of spontaneous CRC.
MDL-811 suppresses CYP24A1 gene transcription, enhances the anti-tumor activity of vitamin D3 in CRC.