Description
Vorinostat, also known as suberoylanilide hydroxamic acid, is a HDAC inhibitor that prevents the deacetylation of histones, therefore altering chromatin structure and inhibiting gene expression. In vitro, vorinostat promotes cell cycle arrest, induces apoptosis, and inhibits cellular proliferation. This compound is effective when administered with other synergistic treatments in glioblastoma stem-like cells and is currently in clinical trials as a potential treatment for a variety of gliomas. Additionally, vorinostat attenuates impairment of fear extinction in animal models and disrupts HIV latency in HIV-infected patients, suggesting it has additional antiviral benefit beyond its anticancer chemotherapeutic activity. Vorinostat also alters RNA splicing activity.
References
Legartová S, Stixová L, Strnad H, et al. Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors. Epigenomics. 2013 Aug;5(4):379-96. PMID: 23895652.
Matsumoto Y, Morinobu S, Yamamoto S, et al. Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder. Psychopharmacology (Berl). 2013 Sep;229(1):51-62. PMID: 23584669.
Silva G, Cardoso BA, Belo H, et al. Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms. PLoS One. 2013;8(1):e53766. PMID: 23320102.
Lee EQ, Puduvalli VK, Reid JM, et al. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03. Clin Cancer Res. 2012 Nov 1;18(21):6032-9. PMID: 22923449.
Archin NM, Liberty AL, Kashuba AD, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482-5. PMID: 22837004.
Asklund T, Kvarnbrink S, Holmlund C, et al. Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors. Anticancer Res. 2012 Jul;32(7):2407-13. PMID: 22753697.
Xu J, Sampath D, Lang FF, et al. Vorinostat modulates cell cycle regulatory proteins in glioma cells and human glioma slice cultures. J Neurooncol. 2011 Nov;105(2):241-51. PMID: 21598070.
