Vorinostat

Vorinostat (rINN) or suberoylanilide hydroxamic acid (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.

Vorinostat is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after treatment with other medicines.^[1]

Approvals and indications

Vorinostat was the first histone deacetylase inhibitor^[2] approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006. It is manufactured by Patheon, Inc., in Mississauga, Ontario, Canada, for Merck & Co., Inc., White House Station, New Jersey.^[3]

Clinical trials

Vorinostat has also been used to treat Sézary syndrome, another type of lymphoma closely related to CTCL.^[4]

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).^[5] 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 cancer (NSCLC) showed improved response rates and increased median progression free survival and overall survival (although the survival improvements were not significant at the P=0.05 level).^[6]

Preclinical investigations

Vorinostat is an interesting target for scientists interested in eradicating HIV from infected persons.^[7] Vorinostat was recently shown to have both in vitro and in vivo effects against latently HIV infected T-Cells.^[8][9]

References

1. ^ "ZOLINZA, Merck's Investigational Medicine for Advanced Cutaneous T-Cell Lymphoma (CTCL), To Receive Priority Review from U.S. Food and Drug Administration" (Press release). Merck & Co.. June 7, 2006. http://www.merck.com/newsroom/press_releases/research_and_development/2006_0607.html. Retrieved 2006-10-06. 
2. ^ HDAC Inhibitors Base (vorinostat)
3. ^ "FDA Approves New Drug for Skin Cancer, Zolinza" (Press release). Food and Drug Administration. October 6, 2006. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01484.html. Retrieved 2006-10-06. 
4. ^ Cuneo A, Castoldi. "Mycosis fungoides/Sezary's syndrome". http://atlasgeneticsoncology.org/Anomalies/MycosFungID2039.html. Retrieved 2008-02-15. 
5. ^ "Vorinostat shows anti-cancer activity in recurrent gliomas" (Press release). Mayo Clinic. June 3, 2007. http://www.eurekalert.org/pub_releases/2007-06/mc-vsa053007.php. Retrieved 2007-06-03. 
6. ^ http://www.rtmagazine.com/reuters_article.asp?id=20091209clin013.html Dec 2009
7. ^ "Study of the Effect of Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART". ClinicalTrials.gov. 2011-03-21. http://www.clinicaltrials.gov/ct2/show/NCT01319383. 
8. ^ Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, Margolis DM (2009). "Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid.". AIDS Res Hum Retroviruses 25 (2): 207–12. doi:10.1089/aid.2008.0191. PMC 2853863. PMID 19239360. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2853863. 
9. ^ Contreras X, Schweneker M, Chen CS, McCune JM, Deeks SG, Martin J et al. (2009). "Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells.". J Biol Chem 284 (11): 6782–9. doi:10.1074/jbc.M807898200. PMC 2652322. PMID 19136668. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19136668. 

See also

• Trichostatin A