Histone Deacetylases (HDAC) Targeted Library

Description

ChemDiv’s Histone Deacetylases (HDAC) Targeted Library contains 9,500 compounds.

Regulation of gene expression is mediated by several mechanisms such as DNA methylation, ATP-dependent chromatin remodeling, and post-translational modifications of histones. The latter mechanism includes dynamic acetylation and deacetylation of ε-amino groups of lysine residues present in the tail of the core histones. Histones are the predominant protein components of chromatin, which stabilize the nucleosome core. They are subjected to a variety of specific post-translational modifications. Reversible acetylation and deacetylation of nucleosomal histones are critical in the modulation of chromatin structure, chromatin function and in the regulation of gene expression. Enzymes responsible for the reversible acetylation/deacetylation processes are histone acetyltransferase (HATs) and histone deacetylases (HDACs), respectively.

Relatively modest progress in understanding pharmacology and clinical role of HDACs has been made since their discovery. Further optimization of these molecules into clinical candidates may yield drugs with enhanced efficacy against cancers, neurodegenerative and inflammatory diseases.

Publications

1. Luckhurst C.A., et al. Potent, Selective, and CNS Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors. ACS Med Chem Lett. 2015;7(1):34 39.

2. Luckhurst CA, et al. Development and characterization of a CNS penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor. Bioorg Med Chem Lett. 2019;29(1):83 88.

3. Blum C.A., Jarpe M.B. Isoform Selective Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancer. Chapter 13, Medicinal Chemistry Reviews 2018; 53:245 264.

4. Wagner F.F., et al. Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors. Bioorg . Med. Chem. 2016;24(18):4008 4015.

5. Ferreira de Freitas R., et al. Identification and Structure Activity Relationship of HDAC6 Zinc Finger Ubiquitin Binding Domain Inhibitors. J. Med. Chem. 2018;61(10):4517 4527.