MC1568
(Synonyms: MC 1568, MC-1568) 目录号 : GC15965
A selective class IIa HDAC inhibitor
Cas No.:852475-26-4
Sample solution is provided at 25 µL, 10mM.
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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.
| Kinase experiment [1]: | |
|
Maize HD2, HD1-B, and HD1-A enzyme inhibition |
The enzyme liberated tritiated acetic acid from the substrate, which was quantified by scintillation counting. IC50 values are results of triple determinations. A 50 μL sample of maize enzyme (at 30 °C) was incubated (30 mins) with 10 μL of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL). Reaction was stopped by addition of 50 μL of 1 M HCl/0.4 M acetate and 800 μL of ethyl acetate. After centrifugation (10000 g, 5 mins), an aliquot of 600 μL of the upper phase was counted for radioactivity in 3 mL of liquid scintillation cocktail. MC1568 was tested at a starting concentration of 40 μM, and active substances were diluted further. NaB, VPA, TSA, SAHA, 85TPX, HC-toxin, and tubacin were used as the reference compounds, and blank solvents were used as negative controls. |
| Cell experiment [2]: | |
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Cell lines |
3T3-L1 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
~ 10 μM; 8 days |
|
Applications |
In 3T3-L1 cells, MC1568 attenuated PPARγ-induced adipogenesis. |
| Animal experiment [2]: | |
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Animal models |
PPRE-Luc transgenic C57BL/6 mice |
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Dosage form |
50 mg/kg; p.o.; q.d., for 7 days |
|
Applications |
In PPRE-Luc transgenic C57BL/6 mice, MC1568 (50 mg/kg) impaired PPARγ signaling mostly in the heart and adipose tissues. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
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. | |
| Cas No. | 852475-26-4 | SDF | |
| 别名 | MC 1568, MC-1568 | ||
| 化学名 | (E)-3-[4-[(E)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-N-hydroxyprop-2-enamide | ||
| Canonical SMILES | CN1C=C(C=C1C=CC(=O)NO)C=CC(=O)C2=CC(=CC=C2)F | ||
| 分子式 | C17H15FN2O3 | 分子量 | 314.31 |
| 溶解度 | ≥ 15.7 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1816 mL | 15.9079 mL | 31.8157 mL |
| 5 mM | 0.6363 mL | 3.1816 mL | 6.3631 mL |
| 10 mM | 0.3182 mL | 1.5908 mL | 3.1816 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet