Trichostatin A

Names

[ Name ]:
Trichostatin A

[Synonym ]:
Antibiotic A-300
2,4-Heptadienamide, 7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-, (2E,4E,6R)-
(2E,4E,6R)-7-[4-(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide
(R)-Trichostatin A
2,4-Heptadienamide, 7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-, (2E,4E,6R)- (9CI)
TSA
2,4-Heptadienamide, 7-(4-(dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-, (2E,4E,6R)-
2,4-Heptadienamide, 7-(4-(dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-
Trichostatin A
7-(4-(Dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide
7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6R-dimethyl-7-oxo-2E,4E-heptadienamide
(2E,4E,6R)-7-[4-(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide

Biological Activity

[Description]:

Trichostatin A is a potent and specific inhibitor of HDAC class I/II, with an IC50 value of 1.8 nM for HDAC.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

Natural Products >> Others

Research Areas >> Cancer

[Target]

HDAC:1.8 nM (IC50)

[In Vitro]

Trichostatin A is a potent and specific inhibitor of HDAC class I/II, with an IC50 value of 1.8 nM for HDAC. Trichostatin A (TSA) inhibits proliferation of eight breast carcinoma cell lines with mean±SD IC50 of 124.4±120.4 nM (range, 26.4-308.1 nM). HDAC inhibitory activity of Trichostatin A is similar in all cell lines with mean IC50 of 2.4±0.5 nM (range, 1.5-2.9 nM)[1]. Trichostatin A (330 nM) increases Gαs protein expression in human myometrial cells, but does not increase Gαs mRNA levels[2]. Trichostatin A (20-75 nM) induces minimal cytotoxicity to adipose-derived stem cells (ADSCs), and enhances the osteogenic differentiation capacity of ADSCs[3]. In addition, Trichostatin A (0, 10, 100, 500 nM) dose-dependently decreases HDAC class I/II activity[4].

[In Vivo]

Trichostatin A (500 μg/kg, s.c.) pronounces antitumor activity without causing any measurable toxicity in doses of up to 5 mg/kg by s.c. injection, in randomized controlled efficacy studies using the N-methyl-N-nitrosourea carcinogen-induced rat mammary carcinoma model[1].

[Cell Assay]

Cells are cultured in a 96-well plate at 1×103 cells per well with 100 μL complete DMEM in the presence or absence of a HDAC inhibitor Trichostatin A for 72 h. Cytotoxicity is measured by performing WST-8 assay using a CCK-8 cell proliferation kit. The 450 nm absorbance is measured with a microplate reader. All experiments are carried out in triplicate and 3 independent experiments are performed[3].

[Animal admin]

Rats[1] Twelve rats are randomized to receive 500 μg/kg Trichostatin A in 50 μL DMSO, or 50 μL DMSO as vehicle control, by s.c. injection twice weekly for 4 weeks. In subsequent studies, 30 rats are randomized to receive Trichostatin A 500 μg/kg in 50 μL DMSO, or 50 μL DMSO as vehicle control, by s.c. injection daily for 4 weeks. Weekly tumor measurements, estimated tumor volumes, and body mass are recorded for each animal. Animals are sacrificed at the end of the 4-week study period; palpable tumors are resected and immediately snap-frozen in liquid nitrogen. Animals with tumors <2 cm in diameter or ulcerating tumors are withdrawn from study[1].

[References]

[1]. Vigushin DM et al. Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. Clin Cancer Res. 2001 Apr;7(4):971-6.

[2]. Karolczak-Bayatti M, et al. Expression of the GTP-Binding Protein Gαs in Human Myometrial Cells is Regulated by Ubiquitination and Protein Degradation: Involvement of Proteasomal Inhibition by Trichostatin A.,Reprod Sci. 2012 Aug 8.

[3]. Hu X, et al. Histone deacetylase inhibitor trichostatin A promotes the osteogenic differentiation of rat adipose-derived stem cells by altering the epigenetic modifications on Runx2 promoter in a BMP signaling-dependent manner.,Stem Cells Dev. 2012 Aug 8.

[4]. Azechi T, et al. Trichostatin A, an HDAC class I/II inhibitor, promotes Pi-induced vascular calcification via up-regulation of the expression of alkaline phosphatase. J Atheroscler Thromb. 2013;20(6):538-47.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Melting Point ]:
141-143ºC

[ Molecular Formula ]:
C₁₇H₂₂N₂O₃

[ Molecular Weight ]:
302.368

[ Exact Mass ]:
302.163055

[ PSA ]:
69.64000

[ LogP ]:
2.77

[ Index of Refraction ]:
1.578

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MI5215000

CHEMICAL NAME :: 2,4-Heptadienamide, 7-(4-(dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7- oxo-

CAS REGISTRY NUMBER :: 58880-19-6

LAST UPDATED :: 198912

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C17-H22-N2-O3

MOLECULAR WEIGHT :: 302.41

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Rodent - rat Embryo

DOSE/DURATION :: 100 ug/L

REFERENCE :: ECREAL Experimental Cell Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.10- 1950- Volume(issue)/page/year: 177,122,1988

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302 + H312 + H332-H315-H317-H319-H335

[ Precautionary Statements ]:
P261-P280-P302 + P352 + P312-P304 + P340 + P312-P333 + P313

[ Personal Protective Equipment ]:
Eyeshields;Gloves;half-mask respirator (US);multi-purpose combination respirator cartridge (US)

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R20/21/22

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NA 1993 / PGIII

[ WGK Germany ]:
3

[ RTECS ]:
MI5215000

[ HS Code ]:
2924299090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2924299090

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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Related Compounds

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