Romidepsin
Bicyclic depsipeptide histone deacetylase inhibitor from Chromobacterium violaceum used for T-cell lymphoma treatment.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C24H36N4O6S2 |
| Molecular Weight | 540.7 Da |
| CAS Number | 128517-07-7 |
| Peptide Class | Bicyclic Depsipeptide |
| Origin | Chromobacterium violaceum |
Structure
Romidepsin (FK228, depsipeptide) is a bicyclic depsipeptide produced by Chromobacterium violaceum. The molecule contains a disulfide bond that is reduced intracellularly to the active thiol form. The reduced form chelates zinc in the HDAC active site. The unique structure includes L-valine, D-cysteine, dehydrobutyrine, and an unusual (Z)-dehydroamino acid.
Mechanism of Action
Romidepsin is a potent class I histone deacetylase (HDAC) inhibitor. After intracellular reduction of the disulfide bond, the free thiol group chelates the zinc ion in the HDAC catalytic site. This causes hyperacetylation of histones, reactivating silenced tumor suppressor genes, cell cycle regulators, and pro-apoptotic pathways in malignant T cells.
Clinical Applications
- Cutaneous T-cell lymphoma: Relapsed or refractory CTCL (Istodax)
- Peripheral T-cell lymphoma: Relapsed or refractory PTCL
- Multiple myeloma: Under investigation
- HIV eradication: Latency reversal (experimental)
Pharmacokinetics
- Half-life: 3 hours
- Protein binding: 92-94%
- Metabolism: CYP3A4 (major), CYP1A1, CYP2B6
- Elimination: Primarily fecal
- Route: IV infusion over 4 hours (days 1, 8, 15 of 28-day cycle)
Safety and Side Effects
Nausea (66%), fatigue (52%), thrombocytopenia (29%), neutropenia (21%), infections (24%), anorexia, dysgeusia, ECG changes (T-wave flattening, ST depression), and QTc prolongation. Electrolyte monitoring required.
References
- Piekarz, R.L., et al. (2009). Phase II trial of romidepsin for CTCL. Journal of Clinical Oncology, 27, 5410-5417.
- Coiffier, B., et al. (2012). Romidepsin for PTCL. Journal of Clinical Oncology, 30, 631-636.
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