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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.
AuthorsKaren M VanderMolen, William McCulloch, Cedric J Pearce, Nicholas H Oberlies
JournalThe Journal of antibiotics (J Antibiot (Tokyo)) Vol. 64 Issue 8 Pg. 525-31 (Aug 2011) ISSN: 0021-8820 [Print] Japan
PMID21587264 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
Chemical References
  • Antineoplastic Agents
  • Biological Products
  • Depsipeptides
  • romidepsin
  • Histone Deacetylases
Topics
  • Antineoplastic Agents (chemistry, isolation & purification, pharmacology, therapeutic use)
  • Biological Products (chemistry, isolation & purification, pharmacology, therapeutic use)
  • Chromobacterium (chemistry, isolation & purification, metabolism)
  • Clinical Trials as Topic
  • Depsipeptides (chemistry, isolation & purification, pharmacology, therapeutic use)
  • Drug Approval
  • Histone Deacetylases (metabolism)
  • Humans
  • Japan
  • Lymphoma, T-Cell, Cutaneous (drug therapy)
  • Models, Molecular
  • Molecular Structure
  • Soil Microbiology
  • United States
  • United States Food and Drug Administration

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