Development of a Potent and Selective HDAC8 Inhibitor

Oscar J Ingham; Ronald M Paranal; William B Smith; Randolph A Escobar; Han Yueh; Tracy Snyder; John A Porco Jr; James E Bradner; Aaron B Beeler

doi:10.1021/acsmedchemlett.6b00239

Development of a Potent and Selective HDAC8 Inhibitor

ACS Med Chem Lett. 2016 Sep 1;7(10):929-932. doi: 10.1021/acsmedchemlett.6b00239. eCollection 2016 Oct 13.

Authors

Oscar J Ingham¹, Ronald M Paranal², William B Smith², Randolph A Escobar¹, Han Yueh¹, Tracy Snyder¹, John A Porco Jr¹, James E Bradner³, Aaron B Beeler¹

Affiliations

¹ Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University , 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
² Department of Medical Oncology, Dana Farber Cancer Institute , Boston, Massachusetts 02215, United States.
³ Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, United States.

Abstract

A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8.

Keywords: HDAC; HDAC8; Histone deacetylase; epigenetic; histone deacetylase 8; triazole.

Grants and funding

R24 GM111625/GM/NIGMS NIH HHS/United States