|Pronunciation||Vorinostat // vorr-IN-oh-stat|
Zolinza (// zoh-LIN-zə
|Trade names||Zolinza, Vorinostat MSD, others|
|Other names||Suberanilohydroxamic acid (SAHA)|
|Drug class||Histone deacetylase inhibitors (HDI)|
|Main uses||Cutaneous T cell lymphoma (CTCL)|
|Side effects||Diarrhea, tiredness, change in taste, low platelets, hair loss, cough, fever|
|By mouth (capsules)|
|Typical dose||400 mg OD|
|Metabolism||Liver glucuronidation and β-oxidation|
CYP system not involved
|Metabolites||vorinostat O-glucuronide, 4-anilino-4-oxobutanoic acid (both inactive)|
|Elimination half-life||~2 hours (vorinostat and O-glucuronide), 11 hours (4-anilino-4-oxobutanoic acid)|
|Chemical and physical data|
|Molar mass||264.325 g·mol−1|
|3D model (JSmol)|
Vorinostat, sold under the brand name Zolinza, is a medication used for cutaneous T cell lymphoma (CTCL). Specifically it is used when the disease persists, gets worse, or comes back during or after two other treatments. It is taken by mouth.
Common side effects include diarrhea, tiredness, change in taste, low platelets, hair loss, cough, and fever. Other severe side effects may include blood clots and high blood sugar. Use during pregnancy may harm the baby. It is a histone deacetylase inhibitors (HDI).
Vorinostat was approved for medical use in the United States in 2006. While it was given orphan medication status in Europe in 2004, in 2009 the application for approval was withdrawn. In the United States it costs about 14,600 USD per month as of 2021.
The typical dose is 400 mg taken once per day.
Mechanism of action
Vorinostat has been shown to bind to the active site of histone deacetylases and act as a chelator for zinc ions also found in the active site of histone deacetylases. Vorinostat's inhibition of histone deacetylases results in the accumulation of acetylated histones and acetylated proteins, including transcription factors crucial for the expression of genes needed to induce cell differentiation. It acts on class I, II and IV of histone deacetylase.
A study suggested that vorinostat also possesses some activity against recurrent glioblastoma multiforme, resulting in a median overall survival of 5.7 months (compared to 4–4.4 months in earlier studies). Further brain tumor trials are planned in which vorinostat will be combined with other drugs.
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