Repurposing bempedoic acid as a histone deacetylase 6 inhibitor

Abstract

The dysregulation of the activity of histone deacetylase 6 (HDAC6) is observed in a number of human diseases. Targeting HDAC6 has been identified as an ideal treatment strategy in epigenetic-based therapies. Bempedoic acid is an FDA-approved cholesterol-lowering medication. In the present study, bempedoic acid was repurposed as an HDAC6 inhibitor for the first time, at least to the best of our knowledge. Bempedoic acid inhibited the activity of HDAC6 in vitro with an IC 50 value of ~0.8 mM. In silico analysis predicted the formation of hydrogen bonds and hydrophobic interactions between HDAC6 residues and bempedoic acid, which may be attributed to its HDAC6 inhibitory potential. The results of the present study provide new opportunities to bring bempedoic acid into epigenetic-based drug discovery platforms.