title: Discovery of histone deacetylase 8 selective inhibitors.
abstract: We have developed an efficient method for synthesizing candidate histone deacetylase (HDAC) inhibitors in 96-well plates, which are used directly in high-throughput screening. We selected building blocks having hydrazide, aldehyde and hydroxamic acid functionalities. The hydrazides were coupled with different aldehydes in DMSO. The resulting products have the previously identified 'cap/linker/biasing element' structure known to favor inhibition of HDACs. These compounds were assayed without further purification. HDAC8-selective inhibitors were discovered from this novel collection of compounds.
authors.affiliation: Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. wtang@pharmacy.wisc.edu
authors.forename: Weiping
authors.initials: W
authors.lastname: Tang
authors.forename: Tuoping
authors.initials: T
authors.lastname: Luo
authors.forename: Edward F
authors.initials: EF
authors.lastname: Greenberg
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
mesh_terms: D001681:Biological Assay; D004789:Enzyme Activation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*
chemical_list: D056572:Histone Deacetylase Inhibitors; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases