World Library  
Flag as Inappropriate
Email this Article

Trichostatin A

Article Id: WHEBN0003181579
Reproduction Date:

Title: Trichostatin A  
Author: World Heritage Encyclopedia
Language: English
Subject: Histone deacetylase inhibitor, Paul Marks (scientist), TSA, Romidepsin, Sirtuin
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Trichostatin A

Trichostatin A
Structural formula of trichostatin A
Space-filling model of the trichostatin A molecule
Systematic (IUPAC) name
7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide
Clinical data
Pregnancy
category
Identifiers
CAS Registry Number  N
ATC code None
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C17H22N2O3
Molecular mass 302.37 g/mol
 N   

Trichostatin A (TSA) is an organic compound that serves as an antifungal antibiotic and selectively inhibits the class I and II mammalian histone deacetylase (HDAC) families of enzymes, but not class III HDACs (i.e., Sirtuins).[1] TSA inhibits the eukaryotic cell cycle during the beginning of the growth stage. TSA can be used to alter gene expression by interfering with the removal of acetyl groups from histones (histone deacetylases, HDAC) and therefore altering the ability of DNA transcription factors to access the DNA molecules inside chromatin. It is a member of a larger class of histone deacetylase inhibitors (HDIs or HDACIs) that have a broad spectrum of epigenetic activities. Thus, TSA has some potential as an anti-cancer drug.[2] One suggested mechanism is that TSA promotes the expression of apoptosis-related genes, leading to cancerous cells surviving at lower rates, thus slowing the progression of cancer.[3] Other mechanisms may include the activity of HDIs to induce cell differentiation, thus acting to "mature" some of the de-differentiated cells found in tumors. HDIs have multiple effects on non-histone effector molecules, so the anti-cancer mechanisms are truly not understood at this time.

TSA inhibits HDACs 1, 3, 4, 6 and 10 with IC50 values around 20 nM.[4]

TSA represses IL (interleukin)-1β/LPS (lipopolysaccharide)/IFNγ (interferon γ)-induced nitric oxide synthase (NOS)2 expression in murine macrophage-like cells but increases LPS-stimulated NOS2 expression in murine N9 and primary rat microglial cells.[5]

TSA has not been tested in clinical trials as of 2013-05-27.[6]

See also

References

  1. ^ Vanhaecke T, Papeleu P, Elaut G, Rogiers V (2004). "Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view". Curr Med Chem 11 (12): 1629–43.  
  2. ^ Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC (2005). "Clinical development of histone deacetylase inhibitors as anticancer agents". Annu Rev Pharmacol Toxicol 45: 495–528.  
  3. ^ Shankar S, Srivastava RK (2008). "Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis". Adv Exp Med Biol. Advances in Experimental Medicine and Biology 615: 261–98.  
  4. ^ http://www.freepatentsonline.com/y2009/0263353.html
  5. ^ Adcock (2007). "HDAC inhibitors as anti-inflammatory agents". 
  6. ^ http://clinicaltrials.gov/ct2/results?term=Trichostatin+A

External links

  • Trichostatin_A Safety data sheet by Fermentek
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from Hawaii eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.