title: A focus on the preclinical development and clinical status of the histone deacetylase inhibitor, romidepsin (depsipeptide, Istodax(®)).
abstract: Romidepsin (Istodax(®), depsipeptide, FR901228, FK228, NSC 630176) is a cyclic peptide, broad-spectrum, potent histone deacetylase inhibitor, with activity mainly against class I histone deacetylase enzymes. In this article, we give an overview of the putative modes of action, such as effects on gene expression, cell cycle regulation, apoptosis induction, DNA repair, protein acetylation and induction of autophagy. Romidepsin has mainly been developed as a therapy for hematologic malignancies and is approved by the US FDA for the treatment of cutaneous T-cell lymphomas. This report outlines the laboratory and clinical development of the compound as a single agent that has more recently been evaluated in combination with other anticancer therapeutics, such as proteasome inhibitors.
authors.affiliation: Haematology Service, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.forename: Mark
authors.initials: M
authors.lastname: Bishton
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
authors.forename: Steven
authors.initials: S
authors.lastname: Grant
authors.forename: Richard L
authors.initials: RL
authors.lastname: Piekarz
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.forename: Becki
authors.initials: B
authors.lastname: Lee
authors.forename: Maria E
authors.initials: ME
authors.lastname: Araujo
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy; D009389:Neovascularization, Pathologic; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D047630:Depsipeptides; C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C087123:romidepsin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases