Romidepsin
Overview
Romidepsin is a cyclic peptide chemotherapeutic agent that is used for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). It is marketed under the brand name Istodax by Celgene.
Chemistry
Romidepsin is a natural product isolated from the bacterium Chromobacterium violaceum. It is a member of the class of compounds known as depsipeptides. The compound is a complex cyclic peptide with a unique structure that includes a disulfide bond and a thioester linkage.
Mechanism of Action
Romidepsin works by inhibiting histone deacetylases (HDACs), a group of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This inhibition results in an accumulation of acetylated histones and acetylated proteins, leading to a change in cell signaling and cell death.
Clinical Use
Romidepsin has been approved by the FDA for the treatment of CTCL and PTCL in patients who have received at least one prior therapy. The drug is administered intravenously.
Side Effects
Common side effects of Romidepsin include nausea, vomiting, fatigue, and loss of appetite. More serious side effects can include infections, heart problems, and changes in the electrical activity of the heart.
Pharmacokinetics
Romidepsin is rapidly distributed in the body following intravenous administration. It is extensively metabolized, primarily by CYP3A4, and excreted in the feces.
Research
Research is ongoing to determine the effectiveness of Romidepsin in treating other types of cancer, including lung cancer, breast cancer, and multiple myeloma.