Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma
Open accessAbstract
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.
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Various KDAC inhibitors have been approved by the FDA, such as vorinostat and romidepsin, but there are currently no approved KAT inhibitors.
“Various KDAC inhibitors [19] have been approved by the FDA such as vorinostat [20] (commonly known as SAHA) and romidepsin [21], but there are currently no approved KAT inhibitors [22–24].”
From Acetylation: a new target for protein degradation in cancer (2025) · cites this paper as [21]
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- [17]Note that the structures of romidepsin (1) and its reduced counterpart (2) were published incorrectly in the review by Grant et al. 58
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Acetylation: a new target for protein degradation in cancer
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- Authors
- VanderMolen, K. M., McCulloch, W., Pearce, C. J., & Oberlies, N. H.
- Affiliations
- University of North Carolina at Greensboro (US)
- Mycosynthetix (United States) (US)
- Corresponding author
- Oberlies, Nicholas H
- Venue
- The Journal of Antibiotics
- Published
- 2011-05-18
- Volume
- 64
- Issue
- 8
- Pages
- 525-531
- ISSN
- 0021-8820 (ISSN-L)
- 1881-1469
- PMC
- PMC3163831
- OpenAlex
- W2082633436
- Cited by
- 333
- References
- 78
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 18 · 2023: 26 · 2022: 23 · 2021: 26 · 2020: 22 · 2019: 23 · 2018: 25 · 2017: 22 · 2016: 27 · 2015: 18 · 2014: 18 · 2013: 12 · 2012: 13
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- The Journal of Antibiotics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- NC Digital Online Collection of Knowledge and Scholarship (The University of North Carolina at Greensboro) (submittedVersion)
- Funders
- Celgene
- National Institutes of Health (CA125066)
- National Cancer Institute (CA-125066, P01CA125066)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Health Sciences › Medicine › Dermatology › Cutaneous lymphoproliferative disorders research
- Keywords
- romidepsin, depsipeptides, histone deacetylase inhibitors, cutaneous T-cell lymphoma, Chromobacterium violaceum, natural product drug discovery, glutathione reduction, drug analogues
- MeSH terms
- Antineoplastic Agents, Biological Products, Chromobacterium, Clinical Trials as Topic, Histone Deacetylases, Humans, Japan, Models, Molecular, Soil Microbiology, United States, United States Food and Drug Administration, Molecular Structure, Lymphoma, T-Cell, Cutaneous, Drug Approval, Depsipeptides
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