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58880-19-6 分子结构
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(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide

ChemBase编号:3905
分子式:C17H22N2O3
平均质量:302.36818
单一同位素质量:302.16304257
SMILES和InChIs

SMILES:
ONC(=O)/C=C/C(=C/[C@H](C(=O)c1ccc(N(C)C)cc1)C)/C
Canonical SMILES:
ONC(=O)/C=C/C(=C/[C@H](C(=O)c1ccc(cc1)N(C)C)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
InChIKey:
RTKIYFITIVXBLE-QEQCGCAPSA-N

引用这个纪录

CBID:3905 http://www.chembase.cn/molecule-3905.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide
IUPAC传统名
trichostatin a
TSA
别名
TSA
Trichostatin A
7-[4-(Dimethylamino)Phenyl]-N-Hydroxy-4,6-Dimethyl-7-Oxo-2,4-Heptadienamide
[R-(E,E)]-7-[4-(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide
Trichostatin A
CAS号
58880-19-6
MDL号
MFCD03848392
PubChem SID
24900542
160967340
46506659
PubChem CID
444732
CHEBI ID
46024
CHEMBL
99
Chemspider ID
392575
DrugBank ID
DB04297
维基百科标题
Trichostatin_A

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 9.567311  质子受体
质子供体 LogD (pH = 5.5) 2.406459 
LogD (pH = 7.4) 2.4066641  Log P 2.409631 
摩尔折射率 90.2389 cm3 极化性 33.119965 Å3
极化表面积 69.64 Å2 可自由旋转的化学键
里宾斯基五规则 true 
Log P 2.36  LOG S -3.85 
溶解度 4.25e-02 g/l 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
ethanol: soluble2 mg/mL expand 查看数据来源
保存条件
-20°C expand 查看数据来源
RTECS编号
MI5215000 expand 查看数据来源
欧盟危险性物质标志
有害性(Harmful) 有害性(Harmful) (Xn) expand 查看数据来源
德国WGK号
3 expand 查看数据来源
危险公开号
20/21/22-36/37/38-43 expand 查看数据来源
安全公开号
26-36 expand 查看数据来源
GHS危险品标识
GHS07 expand 查看数据来源
GHS警示词
Warning expand 查看数据来源
GHS危险声明
H302-H312-H315-H317-H319-H332-H335 expand 查看数据来源
GHS警示性声明
P261-P280-P305 + P351 + P338 expand 查看数据来源
个人保护装置
dust mask type N95 (US), Eyeshields, Faceshields, Gloves expand 查看数据来源
保存温度
-20°C expand 查看数据来源
作用靶点
HDAC expand 查看数据来源
妊娠期药物分类
D—teratogenic expand 查看数据来源
相关基因信息
human ... HDAC1(3065), HDAC4(9759), HDAC6(10013), HDAC8(55869)mouse ... ENSMUSG00000061062(15181)rat ... Hdac7a(84582) expand 查看数据来源
纯度
≥98% (HPLC) expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
生物来源
from Streptomyces sp. expand 查看数据来源
产品质量级别
PREMIUM expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Wikipedia Wikipedia Sigma Aldrich Sigma Aldrich
DrugBank -  DB04297 external link
Drug information: experimental
Selleck Chemicals -  S1045 external link
Research Area
Description Cancer
Biological Activity
Description Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM.
Targets

HDAC

IC50

~1.8 nM [1]

In Vitro Trichostatin A inhibits the proliferation of eight breast carcinoma cell lines including MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3 with mean IC50 of 124.4 nM (range, 26.4-308.1 nM), with more potency against cell lines that express ERα than the ERα-negative cell lines. Trichostatin A inhibits HDAC activity similarly in all the breast cancer cell lines with mean IC50 of 2.4 nM (range, 0.6-2.6 nM), and results in pronounced histone H4 hyperacetylation. [1] Unlike trapoxin (TPX) and Chlamydocin which potently inhibit HDAC1 or HDAC4 but not HDAC6, Trichostatin A inhibits these HDACs to a similar extent with IC50 of 6 nM, 38 nM, and 8.6 nM, respectively. [2] Trichostatin A (100 ng/mL) treatment induces the expression of transforming growth factor β type II receptor (TβRII) in MIA PaCa-2 cells through the recruitment of p300 and PCAF into a Sp1-NF-Y HDAC complex that binds the DNA element of TβRII promoter, which is associated with a concomitant acetylation of Sp1 and an overall decrease in the amount of HDAC associated with the complex. [4]
In Vivo Administration of Trichostatin A at 0.5 mg/kg for 4 weeks displays potent antitumor activity in the N-methyl-N-nitrosourea carcinogen-induced rat mammary carcinoma model, without any measurable toxicity at doses up to 5 mg/kg. [1] Single intraperitoneal doses of 10 mg/kg Trichostatin A in nontransgenic and spinal muscular atrophy (SMA) model mice results in increased levels of acetylated H3 and H4 histones and modest increases in survival motor neuron (SMN) gene expression. Administration of Trichostatin A at 10 mg/kg/day improves survival, attenuates weight loss, and enhances motor behavior in the SMA model mice. [5]
Clinical Trials
Features
Combination Therapy
Description

Loosening-up the chromatin structure induced by pretreatment with Trichostatin A (10 ng/mL) increases the anti-tumor efficiency of VP-16, ellipticine,Doxorubicin, and Cisplatin, with significant sensitization by >10-fold for VP-16 in topoisomerase II inhibitor-resistant D54 cells. Trichostatin A enhances VP-16-induced apoptosis in a p53-dependent and -independent manner. [3]

Protocol
Kinase Assay [1]
In vitro HDAC activity Total cellular extracts are prepared from each breast cancer cell line (MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, or SK-BR-3). A 20 μL crude cell extract (~2.5 ×105 cells), in the presence of varying concentrations of Trichostatin A in 0.1% (v/v) ethanol or 0.1% (v/v) ethanol as vehicle control, are incubated for 60 minutes at 25 °C with 1 μL (~1.5 × 106 cpm) of [3H]acetyl-labeled histone H4 peptide substrate (NH2-terminal residues 2-20) that has been acetylated with [3H]acetic acid, sodium salt (3.7 GBq/mmol) by an in vitro incorporation method. Each 200 μL reaction is quenched with 50 μL of 1 M HCl/0.16 M acetic acid and extracted with 600 μL of ethyl acetate, and released [3H]acetate is quantified by scintillation counting. IC50 values are determined graphically using nonlinear regression to fit inhibition data to the appropriate dose-response curve.
Cell Assay [1]
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
Methods

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.

Animal Study [1]
Animal Models Inbred virgin female (Ludwig/Wistar/Olac) rats bearing tumors induced with NMU
Formulation Dissolved in DMSO
Doses ~5 mg/kg/day
Administration Injection s.c.
References
[1] Vigushin DM, et al. Clin Cancer Res, 2001, 7(4), 971-976.
[2] Furumai R, et al. Proc Natl Acad Sci U S A, 2001, 98(1), 87-92.
[3] Kim MS, et al. Cancer Res, 2003, 63(21), 7291-7300.
[4] Huang W, et al. J Biol Chem, 2005, 280(11), 10047-10054.
[5] Avila AM, et al. J Clin Invest, 2007, 117(3), 659-671.
Sigma Aldrich -  T8552 external link
Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
Biochem/physiol Actions
Inhibits histone deacetylase at nanomolar concentrations; resultant histone hyperacetylation leads to chromatin relaxation and modulation of gene expression. May be involved in cell cycle progression of several cell types, inducing cell growth arrest at both G and G/M phases; may induce apoptosis. Enhances the efficacy of anticancer agents that target DNA.

参考文献

参考文献

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专利

专利

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