CHEBI:46024 - trichostatin A

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ChEBI Name trichostatin A
ChEBI ID CHEBI:46024
Stars This entity has been manually annotated by the ChEBI Team.
Secondary ChEBI IDs CHEBI:39145, CHEBI:46022
Supplier Information ChemicalBook:CB8257301, eMolecules:595091, Selleckchem:Trichostatin-A, ZINC000100014731
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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). However, there are recent reports of the interactions of this molecule with Sirt 6 protein. 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. 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. 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. TSA represses IL (interleukin)-1β/LPS (lipopolysaccharide)/IFNγ (interferon γ)-induced nitric oxide synthase 2 (NOS2) expression in murine macrophage-like cells but increases LPS-stimulated NOS2 expression in murine N9 and primary rat microglial cells. Vorinostat is structurally related to trichostatin A and used to treat cutaneous T cell lymphoma.
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Formula C17H22N2O3
Net Charge 0
Average Mass 302.36826
Monoisotopic Mass 302.16304
InChI InChI=1S/C17H22N2O3/c1-12(5-10-16(20)18-22)11-13(2)17(21)14-6-8-15(9-7-14)19(3)4/h5-11,13,22H,1-4H3,(H,18,20)/b10-5+,12-11+/t13-/m1/s1
InChIKey RTKIYFITIVXBLE-QEQCGCAPSA-N
SMILES C[C@@H](C(=O)c1ccc(cc1)N(C)C)\C=C(C)\C=C\C(=O)NO
Metabolite of Species Details
Streptomyces hygroscopicus (NCBI:txid1912) See: PubMed
Roles Classification
Biological Role(s): bacterial metabolite
Any prokaryotic metabolite produced during a metabolic reaction in bacteria.
EC 3.5.1.98 (histone deacetylase) inhibitor
An EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the function of histone deacetylase (EC 3.5.1.98).
antifungal agent
An antimicrobial agent that destroys fungi by suppressing their ability to grow or reproduce.
(via antibiotic antifungal agent )
antimicrobial agent
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
(via carbocyclic antibiotic )
Application(s): geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
View more via ChEBI Ontology
ChEBI Ontology
Outgoing trichostatin A (CHEBI:46024) has functional parent (R)-trichostatic acid (CHEBI:39158)
trichostatin A (CHEBI:46024) has role bacterial metabolite (CHEBI:76969)
trichostatin A (CHEBI:46024) has role EC 3.5.1.98 (histone deacetylase) inhibitor (CHEBI:61115)
trichostatin A (CHEBI:46024) has role geroprotector (CHEBI:176497)
trichostatin A (CHEBI:46024) is a antibiotic antifungal agent (CHEBI:86478)
trichostatin A (CHEBI:46024) is a hydroxamic acid (CHEBI:24650)
trichostatin A (CHEBI:46024) is a trichostatin (CHEBI:39146)
Incoming trichostatin C (CHEBI:39147) has functional parent trichostatin A (CHEBI:46024)
trichostatin D (CHEBI:39160) has functional parent trichostatin A (CHEBI:46024)
IUPAC Name
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide
Synonyms Sources
(2E,4E,6R)-7-(4-(dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide ChemIDplus
TRICHOSTATIN A PDBeChem
TSA ChemIDplus
Manual Xrefs Databases
C00016002 KNApSAcK
DB04297 DrugBank
HMDB0259177 HMDB
Trichostatin_A Wikipedia
TSN PDBeChem
View more database links
Registry Numbers Types Sources
5291761 Beilstein Registry Number Beilstein
58880-19-6 CAS Registry Number ChemIDplus
Citations
Haritwal T, Goyal N, Gupta N, Parvez S, Agrawala PK (2021)
Trichostatin A mitigates radiation-induced teratogenesis in C57Bl/6 mice.
Mutagenesis 36, 303-309 [PubMed:34086940]
[show Abstract]
Peng C, Lv Z, Hai T, Dai X, Zhou Q (2021)
Differential effects of trichostatin A on mouse embryogenesis and development.
Reproduction (Cambridge, England) 162, 83-94 [PubMed:33983895]
[show Abstract]
Osko JD, Christianson DW (2020)
Binding of inhibitors to active-site mutants of CD1, the enigmatic catalytic domain of histone deacetylase 6.
Acta crystallographica. Section F, Structural biology communications 76, 428-437 [PubMed:32880591]
[show Abstract]
Osko JD, Christianson DW (2019)
Structural Basis of Catalysis and Inhibition of HDAC6 CD1, the Enigmatic Catalytic Domain of Histone Deacetylase 6.
Biochemistry 58, 4912-4924 [PubMed:31755702]
[show Abstract]
You W, Steegborn C (2018)
Structural Basis of Sirtuin 6 Inhibition by the Hydroxamate Trichostatin A: Implications for Protein Deacylase Drug Development.
Journal of medicinal chemistry 61, 10922-10928 [PubMed:30395713]
[show Abstract]
Miyake Y, Keusch JJ, Wang L, Saito M, Hess D, Wang X, Melancon BJ, Helquist P, Gut H, Matthias P (2016)
Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.
Nature chemical biology 12, 748-754 [PubMed:27454931]
[show Abstract]
Decroos C, Bowman CM, Moser JA, Christianson KE, Deardorff MA, Christianson DW (2014)
Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders.
ACS chemical biology 9, 2157-2164 [PubMed:25075551]
[show Abstract]
Park JW, Park SR, Han AR, Ban YH, Yoo YJ, Kim EJ, Kim E, Yoon YJ (2011)
Microbial transformation of trichostatin A to 2,3-dihydrotrichostatin A.
Journal of natural products 74, 1272-1274 [PubMed:21504214]
[show Abstract]
Noh EJ, Lim DS, Jeong G, Lee JS (2009)
An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner.
Biochemical and biophysical research communications 378, 326-331 [PubMed:19038231]
[show Abstract]
Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH (2008)
Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.
The Journal of biological chemistry 283, 11355-11363 [PubMed:18285338]
[show Abstract]
Choi YH (2005)
Induction of apoptosis by trichostatin A, a histone deacetylase inhibitor, is associated with inhibition of cyclooxygenase-2 activity in human non-small cell lung cancer cells.
International journal of oncology 27, 473-479 [PubMed:16010430]
[show Abstract]
Tao D, Lu J, Sun H, Zhao YM, Yuan ZG, Li XX, Huang BQ (2004)
Trichostatin A extends the lifespan of Drosophila melanogaster by elevating hsp22 expression.
Acta biochimica et biophysica Sinica 36, 618-622 [PubMed:15346199]
[show Abstract]
Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP (1999)
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.
Nature 401, 188-193 [PubMed:10490031]
[show Abstract]
Last Modified
27 October 2021