title: A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold.
abstract: Histone deacetylases (HDACs) are enzymes involved in many important biological functions. They have been linked to a variety of cancers, psychiatric disorders, and other diseases. Since small molecules can serve as probes to study the relevant biological roles of HDACs, novel scaffolds are necessary to develop more efficient, selective drug candidates. Screening libraries of molecules may yield structurally diverse probes that bind these enzymes and modulate their functions in cells. Here we report a small molecule with a novel hydroxy-pyrimidine scaffold that inhibits multiple HDAC enzymes and modulates acetylation levels in cells. Analogs were synthesized in an effort to evaluate structure-activity relationships.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Kemp
authors.forename: Qiu
authors.initials: Q
authors.lastname: Wang
authors.forename: Jason H
authors.initials: JH
authors.lastname: Fuller
authors.forename: Nathan
authors.initials: N
authors.lastname: West
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Martinez
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Morse
authors.forename: Michel
authors.initials: M
authors.lastname: Weïwer
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.forename: Angela N
authors.initials: AN
authors.lastname: Koehler
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D011743:Pyrimidines; D006655:Histone Deacetylases; C030986:pyrimidine