title: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma.
abstract: Romidepsin (Istodax), a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the US Food and Drug Administration. This unique natural product was discovered from cultures of Chromobacterium violaceum, a Gram-negative bacterium isolated from a Japanese soil sample. This bicyclic compound acts as a prodrug, its disulfide bridge being reduced by glutathione on uptake into the cell, allowing the free thiol groups to interact with Zn ions in the active site of class I and II HDAC enzymes. Due to the synthetic complexity of the compound, as well as the low yield from the producing organism, analogs are sought to create synthetically accessible alternatives. As a T-cell lymphoma drug, romidepsin offers a valuable new treatment for diseases with few effective therapies.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: VanderMolen
authors.forename: William
authors.initials: W
authors.lastname: McCulloch
authors.forename: Cedric J
authors.initials: CJ
authors.lastname: Pearce
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002861:Chromobacterium / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017277:Drug Approval; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007564:Japan; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008958:Models, Molecular; D015394:Molecular Structure; D012988:Soil Microbiology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D047630:Depsipeptides; C087123:romidepsin; D006655:Histone Deacetylases