title: Profiling technologies for the identification and characterization of small-molecule histone deacetylase inhibitors.
abstract: Histone deacetylases (HDACs) are promising drug targets for treating cancer, neurologic, inflammatory and metabolic diseases. Four small molecule inhibitors of HDACs have gained regulatory approval for treating lymphomas and multiple myelomas. Highly sensitive in vitro and cell-based profiling technologies have been developed to discover HDAC inhibitors (HDACi) and characterize their inhibitory potency, target-binding specificity and kinetics. In particular, proteomic profiling can define the specificity of an inhibitor at a single residue resolution. Chemoproteomic profiling can determine the potency, specificity and binding kinetics of an inhibitor on a specific HDAC complex in cell extracts. As inhibitors with new chemical scaffolds are of particular interest to improve HDAC isoform-specificity and pharmaceutical properties, effective profiling technologies will continue to have important utility. Here we briefly review recent developments of HDAC inhibitor profiling technologies and discuss distinct features of various technologies.
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, UF Health Cancer Center, UF Genetics Institute, Gainesville, FL 32610-0235, United States. Electronic address: dliao@ufl.edu.
authors.forename: Daiqing
authors.initials: D
authors.lastname: Liao
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D056572:Histone Deacetylase Inhibitors; D054852:Small Molecule Libraries; D006655:Histone Deacetylases