Trichostatin A
[CAS# 58880-19-6]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Trichostatin A
• Synonyms: (R)-Trichostatin A; (2E,4E,6R)-7-[4-(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide
• Molecular Formula: C₁₇H₂₂N₂O₃
• Molecular Weight: 302.37
• CAS Registry Number: 58880-19-6
• EC Number: 611-758-2
• SMILES: C[C@H](/C=C(\C)/C=C/C(=O)NO)C(=O)C1=CC=C(C=C1)N(C)C

Properties

• Density: 1.139
• Melting point: 140-143 ºC
• Solubility: 10 mM in DMSO (Expl.)
• Index of refraction: 1.578 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H302-H312-H315-H317-H319-H332-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P272-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Skin sensitization	Skin Sens.	1	H317
Reproductive toxicity	Repr.	2	H361
Skin sensitization	Skin Sens.	1B	H317

Discovory and Applicatios

Trichostatin A is a natural product belonging to the class of hydroxamic acid derivatives, originally isolated from the bacterium Streptomyces hygroscopicus. It is recognized as a potent and selective inhibitor of histone deacetylases (HDACs), enzymes that play a critical role in regulating gene expression by removing acetyl groups from histone proteins. The inhibition of HDACs by trichostatin A leads to increased acetylation of histones, resulting in a more relaxed chromatin structure and altered transcriptional activity.

The discovery of trichostatin A occurred in the late 1970s and early 1980s during the screening of microbial metabolites for antifungal and anticancer properties. Its unique chemical structure and biological activity distinguished it from other compounds, leading to extensive research into its mechanism of action and potential applications. Trichostatin A was one of the first HDAC inhibitors identified and has since been a valuable tool in epigenetics research.

Trichostatin A functions by binding to the active site of HDAC enzymes through its hydroxamic acid moiety, which chelates the zinc ion essential for the catalytic activity of these enzymes. This binding effectively blocks the deacetylation of histones and other non-histone proteins, altering the expression of numerous genes involved in cell cycle regulation, differentiation, apoptosis, and other critical cellular processes.

In biomedical research, trichostatin A is widely used to study the role of histone acetylation in gene regulation, chromatin remodeling, and epigenetic mechanisms. Its ability to modulate gene expression has made it a powerful tool for investigating cancer biology, as aberrant HDAC activity and altered histone acetylation patterns are common features in various cancers. Trichostatin A induces cell cycle arrest, differentiation, and apoptosis in cancer cells, highlighting its potential as an anticancer agent.

Beyond cancer research, trichostatin A has been utilized to explore epigenetic regulation in neurobiology, immunology, and developmental biology. Its effects on gene expression have provided insights into memory formation, immune responses, and stem cell differentiation.

Although trichostatin A itself is primarily used as a research tool, its discovery has paved the way for the development of clinically approved HDAC inhibitors used in cancer therapy, such as vorinostat and romidepsin. These drugs share a similar mechanism of action but have improved pharmacological properties suitable for clinical use.

Trichostatin A is typically supplied as a purified compound soluble in organic solvents, with storage conditions optimized to maintain stability and activity. Careful handling is required due to its potent biological effects.

In summary, trichostatin A is a naturally derived hydroxamic acid compound that functions as a selective inhibitor of histone deacetylases. Its discovery from Streptomyces hygroscopicus has significantly advanced the understanding of epigenetic regulation and contributed to cancer research and drug development. The compound remains a critical reagent in molecular biology and pharmacology for studying chromatin dynamics and gene expression.

References

1998. Histone Deacetylase Inhibitors Up-regulate the Expression of Cell Surface MHC Class-I Molecules in B16/BL6 Cells. The Journal of Antibiotics, 51(1).
DOI: 10.7164/antibiotics.51.89

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(3).
DOI: 10.1016/j.bbrc.2008.11.057

2024. Histone deacetylase inhibitor, Trichostatin A mitigates ionizing radiation induced redox imbalance by regulating NRF2/GPX4/PINK1/PARKIN signaling in mice intestine. Molecular Biology Reports, 51(1).
DOI: 10.1007/s11033-024-09867-x