Elizabeth A. Dunlap/Sandbox 1: Difference between revisions
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== Function == | == Function == | ||
Vorinostat (Zolinza) is an oral drug used as a cancer therapy to treat cutaneous T-cell lymphoma (CTCL) <ref name="one">Duvic, M., & Vu, J. (2007). Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat. Biologics : Targets & Therapy, 1(4), 377–392. doi:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721288/</ref>. Vorinostat, previously known as suberoylanilide hydroxamic acid (SAHA), was the first HDAC inhibitor to be approved by the U.S. Food and Drug Administration on October 6, 2006 <ref name="two">National Cancer Institute. (2013). FDA Approval for Vorinostat. doi:https://www.cancer.gov/about-cancer/treatment/drugs/fda-vorinostat</ref>. Cancer cells tend to over-express histone deacetylase (HDAC). HDAC removes acetyl groups on histones which results in a structural change of chromatin. This change in chromatin structure leads to the repression of gene expression which would result in the proliferation of cancer cells. Vorinostat is an HDAC inhibitor that ultimately stops the uncontrolled growth of the cancer cells. Vorinostat does this by inhibiting the function of HDAC by binding to its zinc-binding site and blocking the removal of acetyl groups. Vorinostat is taken once a day by mouth. The most common side effects were fatigue and gastrointestinal symptoms. <ref name="one"/> | Vorinostat (Zolinza) is an oral drug used as a cancer therapy to treat cutaneous T-cell lymphoma (CTCL) <ref name="one">Duvic, M., & Vu, J. (2007). Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat. Biologics : Targets & Therapy, 1(4), 377–392. doi:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721288/</ref>. Vorinostat, previously known as suberoylanilide hydroxamic acid (SAHA), was the first HDAC inhibitor to be approved by the U.S. Food and Drug Administration on October 6, 2006 <ref name="two">National Cancer Institute. (2013). FDA Approval for Vorinostat. doi:https://www.cancer.gov/about-cancer/treatment/drugs/fda-vorinostat</ref>. Cancer cells tend to over-express histone deacetylase (HDAC). HDAC removes acetyl groups on histones which results in a structural change of chromatin. This change in chromatin structure leads to the repression of gene expression which would result in the proliferation of cancer cells. <scene name='75/756751/Saha/1'>Vorinostat</scene> is an HDAC inhibitor that ultimately stops the uncontrolled growth of the cancer cells. Vorinostat does this by inhibiting the function of HDAC by binding to its zinc-binding site and blocking the removal of acetyl groups. Vorinostat is taken once a day by mouth. The most common side effects were fatigue and gastrointestinal symptoms. <ref name="one"/> | ||
== Structure == | == Structure == | ||
The IUPAC name for Zolinza is N'-hydroxy-N-phenyloctanediamide<ref name="three">Grant, S., Easley, C., & Kirkpatrick, P. (2007) Fresh from the Pipline, Vorinostat. Nature Publishing Group. doi:http://www.nature.com/nrd/journal/v6/n1/full/nrd2227.html</ref>. Vorinostat has a molecular formula of C<sub>14</sub>H<sub>20</sub>N<sub>2</sub>O<sub>3</sub> and a molecular weight of 263.32 g/mol<ref name="four">Bubna, A. (2015) Vorinostat - An overview. Indian J Dermatol. 60:419. | |||
doi:http://www.e-ijd.org/article.asp?issn=0019-5154;year=2015;volume=60;issue=4;spage=419;epage=419;aulast=Bubna</ref>. It has a melting point ranging from 159 to 160.5 degrees Celsius. This HDAC inhibitor is completely soluble in dimethylsulfide, somewhat soluble in water, ethanol, isopropanol, and acetone, and insoluble in methylene chloride<ref name="five">Merck & Co Inc. (2015). Highlights of Prescribing Information: Zolinza. doi:https://www.merck.com/product/usa/pi_circulars/z/zolinza/zolinza_pi.pdf</ref>. It’s pH value in water solution is 6.6 with a pKa value of 9.2 <ref name="four"/>. All HDAC inhibitors consist of three different domains: a cap group that interacts with the binding pocket, a zinc binding domain (ZBD) that matches to the active site of the zinc ion, and a linker which binds the two together<ref name="six">Mottamal, M., Zheng, S., Huang, T. L., & Wang, G. (2015). Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents. Molecules, Vol 20, Iss 3, Pp 3898-3941. doi:www.mdpi.com/1420-3049/20/3/3898/pdf</ref>. | doi:http://www.e-ijd.org/article.asp?issn=0019-5154;year=2015;volume=60;issue=4;spage=419;epage=419;aulast=Bubna</ref>. It has a melting point ranging from 159 to 160.5 degrees Celsius. This HDAC inhibitor is completely soluble in dimethylsulfide, somewhat soluble in water, ethanol, isopropanol, and acetone, and insoluble in methylene chloride<ref name="five">Merck & Co Inc. (2015). Highlights of Prescribing Information: Zolinza. doi:https://www.merck.com/product/usa/pi_circulars/z/zolinza/zolinza_pi.pdf</ref>. It’s pH value in water solution is 6.6 with a pKa value of 9.2 <ref name="four"/>. All HDAC inhibitors consist of three different domains: a cap group that interacts with the binding pocket, a zinc binding domain (ZBD) that matches to the active site of the zinc ion, and a linker which binds the two together<ref name="six">Mottamal, M., Zheng, S., Huang, T. L., & Wang, G. (2015). Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents. Molecules, Vol 20, Iss 3, Pp 3898-3941. doi:www.mdpi.com/1420-3049/20/3/3898/pdf</ref>. | ||