Trichostatin A

Trichostatin A

Clinical data
Pregnancy category	Teratogenic
ATC code	None
Identifiers
IUPAC name (2E,4E,6R)-7-[4-(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide
CAS Number	58880-19-6 N
PubChem CID	444732
IUPHAR/BPS	7005
DrugBank	DB04297 Y
ChemSpider	392575 Y
ChEBI	CHEBI:46024 Y
ChEMBL	CHEMBL99 Y
ECHA InfoCard	100.107.856
Chemical and physical data
Formula	C17H22N2O3
Molar mass	302.37 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(NO)\C=C\C(=C\[C@H](C(=O)c1ccc(N(C)C)cc1)C)C
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 Y Key:RTKIYFITIVXBLE-QEQCGCAPSA-N Y
NY (what is this?)

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). 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.