Pronunciation vor-IN-oh-stat AHFS/Drugs.com Monograph Routes ofadministration Oral (capsules) CAS ID 149647-78-9 DrugBank DB02546 | Trade names Zolinza MedlinePlus a607050 Molar mass 264.32 g/mol Formula C14H20N2O3 License data US FDA: Vorinostat | |
Pregnancycategory US: D (Evidence of risk) Biological half-life ~2 hours (vorinostat and O-glucuronide), 11 hours (4-anilino-4-oxobutanoic acid) | ||
Vorinostat (rINN) also known as suberanilohydroxamic acid (suberoyl+anilide+hydroxamic acid abbreviated as SAHA) is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) have a broad spectrum of epigenetic activities.
Contents
- Gfp expression in primary human astrocytes vorinostat
- Medical uses
- Mechanism of action
- Clinical trials
- Preclinical investigations
- References
Vorinostat is marketed under the name Zolinza (zo-LINZ-ah) by Merck for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after two systemic therapies. The compound was developed by Columbia University chemist Ronald Breslow and Memorial Sloan-Kettering researcher Paul Marks.
Gfp expression in primary human astrocytes vorinostat
Medical uses
Vorinostat was the first histone deacetylase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006. It also failed to demonstrate efficacy in treating acute myeloid leukemia in a phase II study.
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.
Clinical trials
Vorinostat has also been used to treat Sézary syndrome, another type of lymphoma closely related to CTCL.
A recent 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.
Including vorinostat in treatment of advanced non-small-cell lung carcinoma (NSCLC) showed improved response rates and increased median progression free survival and overall survival.
It has given encouraging results in a phase II trial for myelodysplastic syndromes in combination with idarubicin and cytarabine.
Preclinical investigations
Vorinostat is an interesting target for scientists interested in eradicating HIV from infected persons. Vorinostat was recently shown to have both in vitro and in vivo effects against latently HIV infected T cells.
Vorinostat also has shown some activity against the pathophysiological changes in α1-antitrypsin deficiency and cystic fibrosis. Recent evidences also indicate Vorinostat as a therapeutic tool for Niemann-Pick type C1 (NPC1), a rare lysosomal lipid storage disease.