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.

KEYWORDS::

• apoptosis
• hematology
• histone deacetylase inhibitor
• malignancy
• romidepsin

Financial & competing interests disclosure

SJ Harrison and HM Prince have received grant funding and honoraria from Celgene. SE Bates recieves funding via Cooperative Research and Development Agreement between NCI and Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

SJ Harrison and HM Prince have received grant funding and honoraria from Celgene. SE Bates recieves funding via Cooperative Research and Development Agreement between NCI and Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.