Repurposing bempedoic acid as a histone deacetylase 6 inhibitor

Ediriweera,Meran Keshawa; Rajan,Priyanka; Cho,Somi Kim

doi:10.3892/ije.2023.15

Repurposing bempedoic acid as a histone deacetylase 6 inhibitor

Authors:
- Meran Keshawa Ediriweera
- Priyanka Rajan
- Somi Kim Cho
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Affiliations: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Colombo 008, Sri Lanka, Subtropical‑Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Republic of Korea
Published online on: April 18, 2023 https://doi.org/10.3892/ije.2023.15
Article Number: 1
Copyright: © Ediriweera et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 IC₅₀ 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.

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