1. Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron
- Author
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Madeleine C. M. Gemmell, Louis M. Rendina, Jan Kahlert, and Poya Kavianpour
- Subjects
Boron Compounds ,inorganic chemicals ,medicine.drug_class ,Histone Deacetylase 2 ,010402 general chemistry ,01 natural sciences ,Biochemistry ,HDAC2 inhibitors ,chemistry.chemical_compound ,0302 Inorganic Chemistry ,medicine ,Humans ,Epigenetics ,Molecular Biology ,IC50 ,Vorinostat ,chemistry.chemical_classification ,0304 Medicinal and Biomolecular Chemistry ,Molecular Structure ,010405 organic chemistry ,Histone deacetylase 2 ,Organic Chemistry ,Histone deacetylase inhibitor ,HDAC2 ,0104 chemical sciences ,Histone Deacetylase Inhibitors ,Enzyme ,chemistry ,Molecular Medicine ,Histone deacetylase ,boron ,03 Chemical Sciences ,Boronic acid ,medicine.drug - Abstract
Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour-suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron-based (boronic acid, boronate ester and closo-1,2-carborane) HDAC2 inhibitors with IC50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC50 =40.6±1.5 nM), followed closely by the 1,2-closo-carborane (IC50 =42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold-standard HDAC pan-inhibitor vorinostat (1) toward this particular HDAC isoform.
- Published
- 2020
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