title: Succinimide hydroxamic acids as potent inhibitors of histone deacetylase (HDAC).
abstract: A series of succinimide hydroxamic acids was prepared and evaluated in vitro for HDAC inhibition and tumor cell antiproliferation. While the original macrocyclic analogue 6 was quite potent in both assays, several appropriately substituted non-macrocyclic succinimides, such as 23, were equipotent.
authors.affiliation: Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. mike.curtin@abbott.com
authors.forename: Michael L
authors.initials: ML
authors.lastname: Curtin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Garland
authors.forename: H Robin
authors.initials: HR
authors.lastname: Heyman
authors.forename: Robin R
authors.initials: RR
authors.lastname: Frey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
authors.forename: Junling
authors.initials: J
authors.lastname: Li
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Pease
authors.forename: Keith B
authors.initials: KB
authors.lastname: Glaser
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Marcotte
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D007202:Indicators and Reagents; D020014:K562 Cells; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D013388:Succinimides; D006655:Histone Deacetylases