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AR-42 (OSU-HDAC42)HDAC抑制剂

AR-42 (OSU-HDAC42)

产品编号:A4104
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规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥1,300.00 现货
2mg ¥500.00 现货
5mg ¥1,050.00 现货
10mg ¥1,900.00 现货
50mg ¥5,900.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1.Bagnall NH, Hines BM, et al. "Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID:28110187
2.Park, Jeenah, Scott Thomas, and Pamela N. Munster. "Epigenetic modulation with histone deacetylase inhibitors in combination with immunotherapy." Epigenomics 7.4 (2015): 641-652. PMID:26111034

质量控制

化学结构

AR-42 (OSU-HDAC42)

相关生物数据

AR-42 (OSU-HDAC42)

相关生物数据

AR-42 (OSU-HDAC42)

相关生物数据

AR-42 (OSU-HDAC42)

AR-42 (OSU-HDAC42) Dilution Calculator

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AR-42 (OSU-HDAC42) Molarity Calculator

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化学性质

CAS号 935881-37-1 SDF Download SDF
化学名 N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide
SMILES CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO
分子式 C18H20N2O3 分子量 312.36
溶解度 ≥15.62 mg/mL in DMSO, <2.2 mg/mL in EtOH, <2.34 mg/mL in H2O 储存条件 Store at -20°C
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。

生物活性

描述 AR-42是HDAC的抑制剂,IC50值为30 nM。
靶点 HDAC          
IC50 30 nM          

实验操作

激酶实验 [1]:

体外HDAC试验

使用HDAC测定试剂盒分析HDAC活性。DU-145核提取物具有丰富的HDAC活性,可以使结合于链霉素琼脂糖珠的生物素化[3H]-乙酰组蛋白H4多肽脱去乙酰基。通过测量释放到上清液中的[3H]-乙酸盐计算HDAC活性。以丁酸钠 (0.25 ~ 1 mM) 为阳性对照。

细胞实验 [1]:

细胞系

DU-145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 °C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 °C可放置数月。

反应条件

10 ~ 1000 nM;96小时

实验结果

AR-42抑制DU-145细胞生长,其IC50值为0.11 μM。

动物实验 [2]:

动物模型

皮下接种PC-3细胞的雄性NCr无胸腺裸鼠

给药剂量

25 mg/kg,每日1次,或50 mg/kg,每日1次,隔天给药;口服给药,持续28天

实验结果

在剂量为25 mg和50 mg下,AR-42抑制PC-3肿瘤异种移植物生长(分别为52%和67%)。

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]. Lu Q, Wang DS, Chen CS, Hu YD, Chen CS. Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005 Aug 25;48(17):5530-5.

[2]. Kulp SK, Chen CS, Wang DS, Chen CY, Chen CS. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Clin Cancer Res. 2006 Sep 1;12(17):5199-206.

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研究更新

1. Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination. J Mol Med (Berl). 2013 Oct;91(10):1221-31. doi: 10.1007/s00109-013-1054-9. Epub 2013 May 29.
Abstract
The treatment of AR-42 and CRT/E7 DNA vaccine resulted in longer survival, decreased tumor growth and enhanced E7-specific immune response in HPV-16 E7-expressing murine TC-1 tumor-bearing mice compared to AR-42 or CRT/E7 DNA vaccine alone, which indicates AR-42 is capable of enhancing the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Moreover, AR-42 increased the surface expression of MHC class I molecules in TC-1 cells and its susceptibility to the cytotoxicity of E7-specific T cells.
2. Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia. Leukemia. 2013 Apr;27(4):871-8. doi: 10.1038/leu.2012.342. Epub 2012 Nov 26.
Abstract
AR-42 is a potent HDACI in AML that increases miR-29b levels and induces down-regulation of known miR-29n targets. The AR-42-and-then-decitabine regime exhibited stronger anti-leukemic activity in vitro and in vivo than the decitabine-and-then AR-42 regime and each mono-therapy.
3. Histone deacetylase inhibitor AR-42 differentially affects cell-cycle transit in meningeal and meningioma cells, potently inhibiting NF2-deficient meningioma growth. Cancer Res. 2013 Jan 15;73(2):792-803. doi: 10.1158/0008-5472.CAN-12-1888. Epub 2012 Nov 14.
Abstract
Although it inhibited cell proliferation in both Ben-Men-1 and meningeal cells through increasing the expression of p16(INK4A), P21(CIP1/WAF1) and p27(KIP1), AR-42 induced cell arrest at G(2)-M and significantly reduced cyclin B expression in Ben-Men-1 cells whereas induced cell arrest at G(1) and reduced expression of proliferating cell nuclear antigen and cyclins D1, E and A in meningeal cells. Additionally, AR-42 decreased the expression of Aurora A, Aurora B and Bcl(XL),increased Bim expression and caused regression of Ben-Men-1-LucB tumors.
4. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells. Int J Cancer. 2011 Jul 1;129(1):204-13. doi: 10.1002/ijc.25660. Epub 2010 Dec 1.
Abstract
AR-42 exhibited cytotoxicity against MM cells at a mean LC(50) of 0.18 ± 0.06 μmol/l, which induced apoptosis with cleavage of caspases 8,9 and 3 and affected gp130/STAT-3 pathway through down-regulation of expression of gp130 and STAT3-regulated targets and inhibition of STAT3 activation.

产品描述

AR-42 (OSU-HDAC42),hydroxamate-tethered phenylbutyrate的衍生物,是一种新型有效的组蛋白去乙酰化酶(HDAC)抑制剂,有效抑制HDAC的活性,IC50值为16 nM,诱导组蛋白H3乙酰化,α-微管蛋白乙酰化和p21的上调,这些被视为HDAC抑制的标志性指标。据报道,AR-42调节几个细胞凋亡抑制剂以及细胞存活调节剂,包括Akt、Bcl-xL、Bax、Ku70和Surviving,通过对PI3K/Akt信号通路的至少部分抑制,对多种肿瘤类型具有有效的抗肿瘤活性,如人前列腺癌和肝癌。

参考文献:
Matthew L.  Bush†, Janet Oblinger†, Victoria Brendel, Griffin Santarelli, Jie Huang, Elena M. Akhmametyeva, Sarah S. Burns, Justin Wheeler, Jeremy Davis, Charles W. Yates, Abhik R. Chaudhury, Samuel Kulp, Ching-Shih Chen, Long-Sheng Chang, D. Bradley Welling, and Abraham Jacob. AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas. Neuro-Oncology 13(9):983–999, 2011
Aaron M.  Sargeant, Robert C. Rengel, Samuel K. Kulp, et al. OSU-HDAC42, a Histone Deacetylase Inhibitor, Blocks Prostate Tumor Progression in the Transgenic Adenocarcinoma of the Mouse Prostate Model Cancer Res 2008;68:3999-4009.
Qiang Lu, Da-Sheng Wang, Chang-Shi Chen, Yuan-Dong Hu, and Ching-Shih Chen.  Structure-Based Optimization of Phenylbutyrate-Derived Histone DeacetylaseInhibitors. J. Med. Chem. 2005, 48, 5530-5535