Vorinostat

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Lua error in Module:Infobox at line 314: malformed pattern (missing ']'). 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.

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] The compound was developed by Columbia University chemist Ronald Breslow and Memorial Sloan-Kettering researcher Paul Marks.[2][3]

Medical uses

Vorinostat was the first histone deacetylase inhibitor[4] approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006.[5] It also failed to demonstrate efficacy in treating acute myeloid leukemia in a phase II study.[6]

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 [7] 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.[7]

Clinical trials

Vorinostat has also been used to treat Sézary syndrome, another type of lymphoma closely related to CTCL.[8]

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).[9] 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).[10]

It has given encouraging results in a phase II trial for myelodysplastic syndromes in combination with Idarubicin and Cytarabine.[11]

Preclinical investigations

Vorinostat is an interesting target for scientists interested in eradicating HIV from infected persons.[12] Vorinostat was recently shown to have both in vitro and in vivo effects against latently HIV infected T-cells.[13][14]

Vorinostat also has shown some activity against the pathophysiological changes in Alpha 1-antitrypsin deficiency[15] and Cystic Fibrosis.[16]

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lee JH1, Mahendran A, Yao Y, Ngo L, Venta-Perez G, Choy ML, Kim N, Ham WS, Breslow R, Marks PA. "Development of a histone deacetylase 6 inhibitor and its biological effects." Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15704-9. doi: 10.1073/pnas.1313893110
  3. ↑ Marks, P.A., Breslow, R. B., "Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug" Nature Biotechnology, 2007, 25 doi:10.1038/nbt1272
  4. ↑ HDAC Inhibitors Base (vorinostat)
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ 7.0 7.1 Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ http://www.rtmagazine.com/reuters_article.asp?id=20091209clin013.html Dec 2009. URL dead Jan 2012
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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