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MC1568

现货
Catalog No.
A4094
II类HDAC抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 500.00
现货
25mg
¥ 1,000.00
现货

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Background

MC1568, a derivative of (Aryloxopropenyl)pyrrolyl hydroxyamide, is a novel, potent and specific inhibitor of class II histone deacetylase (HDAC), including two subclasses IIa (HDAC4, HDAC5, HDAC6, HDAC7 and HDAC9) and IIb (HDAC6 and HDAC 10), that exhibits strong inhibition against maize class II HDAC with 50% inhibition concentration IC50 value of 22 μM. MC1568 has been found to tissue-selectively inhibits HDAC and arrest myogenesis in cultured muscle cells through three possible mechanisms, including decreasing the expression of myocyte enhancer factor 2D, stabilizing the HDAC-HDAC3-MEF2D complex and inhibiting the acetylation of differentiation-induced MEF2D. Moreover, MC1568 is able to interfere with RAR- and PPARγ-mediated differentiation-inducing signaling pathways.

Reference

Mai A, Massa S, Pezzi R, Simeoni S, Rotili D, Nebbioso A, Scognamiglio A, Altucci L, Loidl P, Brosch G. Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. J Med Chem. 2005 May 5;48(9):3344-53.

Nebbioso A, Dell'Aversana C, Bugge A, Sarno R, Valente S, Rotili D, Manzo F, Teti D, Mandrup S, Ciana P, Maggi A, Mai A, Gronemeyer H, Altucci L. HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation. J Mol Endocrinol. 2010 Oct;45(4):219-28. doi: 10.1677/JME-10-0043. Epub 2010 Jul 16.

Nebbioso A, Manzo F, Miceli M, Conte M, Manente L, Baldi A, De Luca A, Rotili D, Valente S, Mai A, Usiello A, Gronemeyer H, Altucci L. Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes. EMBO Rep. 2009 Jul;10(7):776-82. doi: 10.1038/embor.2009.88. Epub 2009 Jun 5.

文献引用

1.Hari Prasad, Rajini Rao. "The Amyloid Clearance Defect in ApoE4 Astrocytes is Corrected by Epigenetic Restoration of NHE6." bioRxiv. 2018.January. 4
2. Griffin EA Jr, Melas PA, et al. "Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5." Sci Adv. 2017 Nov 1;3(11):e1701682. PMID:29109977
3. Ha, Soon-Duck, et al. "Inhibition of IL-1β Expression by Anthrax Lethal Toxin is Reversed by HDAC8 Inhibition in Murine Macrophages." Journal of Biological Chemistry (2016): jbc-M115. PMID:26912657

Chemical Properties

StorageStore at -20°C
M.Wt314.31
Cas No.852475-26-4
FormulaC17H15FN2O3
SynonymsMC 1568, MC-1568
Solubility≥15.7 mg/mL in DMSO, <1.58 mg/mL in H2O, <1.57 mg/mL in EtOH
Chemical Name(E)-3-[4-[(E)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-N-hydroxyprop-2-enamide
SDFDownload SDF
Canonical SMILESCN1C=C(C=C1C=CC(=O)NO)C=CC(=O)C2=CC(=CC=C2)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

玉米HD2, HD1-B,和 HD1-A酶抑制

酶使氚化乙酸从底物中释放,使用闪烁计数器定量。IC50值取自三次平行测定结果。将50 μL玉米酶样品(在30 °C下)与10 μL总[3H]醋酸盐标记的鸡网状细胞组蛋白 (2 mg/mL) 一起孵育30分钟。加入50 μL of 1 M HCl/0.4 M乙酸盐和800 μL乙酸乙酯终止上述反应。离心(10000 g,5分钟)后,将600 μL上清液加入到3 mL液体闪烁鸡尾酒中,测定其放射性。MC1568的初始浓度40 μM,再被逐步稀释。以NaB、VPA、TSA、SAHA、85TPX、HC-toxin和tubacin为参考物,空白溶剂作为阴性对照。

细胞实验 [2]:

细胞系

3T3-L1细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

~ 10 μM;8天

实验结果

在3T3-L1细胞中,MC1568减少PPARγ诱导的脂肪生成

动物实验 [2]:

动物模型

PPRE-Luc转基因C57BL/6小鼠

给药剂量

50 mg/kg;口服给药;每日1次,持续7天

实验结果

在PPRE-Luc转基因C57BL/6小鼠中,MC1568 (50 mg/kg) 主要损害心脏和脂肪组织的PPARγ信号。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Mai A, Massa S, Pezzi R, Simeoni S, Rotili D, Nebbioso A, Scognamiglio A, Altucci L, Loidl P, Brosch G. Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. J Med Chem. 2005 May 5;48(9):3344-53.

[2]. Nebbioso A, Dell'Aversana C, Bugge A, Sarno R, Valente S, Rotili D, Manzo F, Teti D, Mandrup S, Ciana P, Maggi A, Mai A, Gronemeyer H, Altucci L. HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation. J Mol Endocrinol. 2010 Oct;45(4):219-28.

生物活性

描述 MC1568是一种选择性的HDAC抑制剂,作用于玉米HD1-A,IC50值为100 nM,对HD1-A的选择性比HD1-B高34倍。
靶点 HD1-A (Maize) HD1-B (Maize)        
IC50 100 nM 3400 nM        

质量控制

化学结构

MC1568

相关生物数据

MC1568

相关生物数据

MC1568

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MC1568

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MC1568