Trichostatin A
Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.
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Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to
24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
Need more advice on solubility, usage and handling? Please email to: service@chemfaces.com
The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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Proc Natl Acad Sci U S A, 2001 Jan 2;98(1):87-92.
Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin.[Pubmed:
11134513]
Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs).
METHODS AND RESULTS:
TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar concentrations. The HDAC1 inhibition by CHAP1 was reversible as it was by TSA, in contrast to the irreversible inhibition by TPX. CHAP with an aliphatic chain length of five, which corresponded to that of acetylated lysine, was stronger than those with other lengths. These results suggest that TPX is a substrate mimic and that the replacement of the epoxyketone with the hydroxamic acid converted TPX to an inhibitor chelating the zinc like TSA. Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited these HDACs to a similar extent. HDAC6 inhibition by TPX at a high concentration was reversible, probably because HDAC6 is not alkylated by TPX. We further synthesized the counterparts of all known naturally occurring cyclic tetrapeptides containing the epoxyketone. HDAC1 was highly sensitive to all these CHAPs much more than HDAC6, indicating that the structure of the cyclic tetrapeptide framework affects the target enzyme specificity.
CONCLUSIONS:
These results suggest that CHAP is a unique lead to develop isoform-specific HDAC inhibitors.
Clin Cancer Res,2001 Apr;7(4):971-6.
Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.[Pubmed:
11309348]
Cell lines: MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3
Concentrations: Dissolved in absolute ethanol, final concentrations ~10 μM
Incubation Time: 96 hours
Method:
Cells are exposed to various concentrations of Trichostatin A for 96 hours. After treatment, cell proliferation is estimated using the sulforhodamine B colorimetric assay. Cell viability is determined by trypan blue exclusion.
Clin Cancer Res,2001 Apr;7(4):971-6.
Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.[Pubmed:
11309348]
Animal Models: Inbred virgin female (Ludwig/Wistar/Olac) rats bearing tumors induced with NMU
Dosages: ~5 mg/kg/day
Administration: Injection s.c.
