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Zolinza (VORINOSTAT)
Zolinza works by blocking the action of histone deacetylase 6, an enzyme that removes acetyl groups from histones, leading to changes in gene expression.
Zolinza (Vorinostat) is a small molecule Histone Deacetylase Inhibitor (HDACi) developed by Merck and currently owned by MSD Sub Merck. It targets Histone Deacetylase 6 (HDAC6) and was FDA-approved in 2006 for the treatment of Primary Cutaneous T-cell lymphoma. Zolinza has a short half-life of 0.76 hours and moderate bioavailability of 43%. It remains a patented product with no generic manufacturers available. Key safety considerations include its potential for hepatotoxicity and thrombocytopenia.
At a glance
| Generic name | VORINOSTAT |
|---|---|
| Sponsor | Merck & Co. |
| Drug class | Histone Deacetylase Inhibitor [EPC] |
| Target | Histone deacetylase 6 |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2006 |
Mechanism of action
Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50<86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. Hypoacetylation of histones is associated with condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat
Approved indications
- Primary cutaneous T-cell lymphoma
Common side effects
- Fatigue
- Diarrhea
- Nausea
- Thrombocytopenia
- Anorexia
- Dysgeusia
- Pulmonary embolism
- Anemia
- Squamous cell carcinoma
- Muscle spasms
- Alopecia
- Dry mouth
Drug interactions
- warfarin
Key clinical trials
- Oral SAHA (Suberoylanilide Hydroxamic Acid) in Advanced Cutaneous T-cell Lymphoma (0683-001) (PHASE2)
- Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia (PHASE2)
- Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma (PHASE1)
- Vorinostat in Treating Patients With Metastatic Melanoma of the Eye (PHASE2)
- Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas (PHASE1)
- Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia (PHASE1,PHASE2)
- A Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (PHASE1,PHASE2)
- Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer (PHASE1)
Patents
| Patent | Expiry | Type |
|---|---|---|
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Zolinza CI brief — competitive landscape report
- Zolinza updates RSS · CI watch RSS
- Merck & Co. portfolio CI