Biomaterial Database

Development and therapeutic implications of selective histone deacetylase 6 inhibitors. 2013

Jay H Kalin, and Joel A Bergman

Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Illinois 60612, United States. jkalin1@jhmi.edu

This Perspective provides an in depth look at the numerous disease states in which histone deacetylase 6 (HDAC6) has been implicated. The physiological pathways, protein-protein interactions, and non-histone substrates relating to different pathological conditions are discussed with regard to HDAC6. Furthermore, the compounds and methods used to modulate HDAC6 activity are profiled. The latter half of this Perspective analyzes reported HDAC6 selective inhibitors in terms of structure, potency, and selectivity over the other HDAC isoforms with the intent of providing a comprehensive overview of the molecular tools available. Potential obstacles and future directions of HDAC6 research are also presented.

UI	MeSH Term	Description	Entries
D004194	Disease	A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.	Diseases
D006655	Histone Deacetylases	Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.	Class I Histone Deacetylases,Class II Histone Deacetylases,HDAC Proteins,Histone Deacetylase,Histone Deacetylase Complexes,Complexes, Histone Deacetylase,Deacetylase Complexes, Histone,Deacetylase, Histone,Deacetylases, Histone
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073864	Histone Deacetylase 6	A class II histone deacetylase that removes acetyl groups from N-terminal LYSINES of HISTONE H2A; HISTONE H2B; HISTONE H3; and HISTONE H4. It plays a critical role in EPIGENETIC REPRESSION and regulation of GENETIC TRANSCRIPTION, as well as CELL MOTILITY through deacetylation of TUBULIN. It also targets misfolded proteins for clearance by AUTOPHAGY when MOLECULAR CHAPERONE-mediated folding is overwhelmed.
D056572	Histone Deacetylase Inhibitors	Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.	HDAC Inhibitor,HDAC Inhibitors,Histone Deacetylase Inhibitor,Deacetylase Inhibitor, Histone,Deacetylase Inhibitors, Histone,Inhibitor, HDAC,Inhibitor, Histone Deacetylase,Inhibitors, HDAC,Inhibitors, Histone Deacetylase