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Belinostat (PXD101)

现货
Catalog No.
A4096
羟肟酸型HDAC抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
现货
10mg
¥ 650.00
现货
50mg
¥ 2,050.00
现货
100mg
¥ 3,150.00
现货
200mg
¥ 5,900.00
现货

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Background

Belinostat (also known as PXD101) is a novel and potent hydroxamate-type inhibitor of histone deacetylase (HDAC) that inhibits the activity of HDAC in Hela cell extracts with 50% inhibition concentration IC50 value of 27 nM. Belinostat has been found to significantly increase the acetylation of histones H3 and H4 and exerts cytotoxicity in a wide range of tumor cell lines. In the treatment of urothelial carcinoma cell lines, belinostat dose-dependently inhibits proliferation in 5637, T24, J82 and RT4 cells with IC50 values of 1.0 μM, 3.5 μM, 6.0 μM and 10 μM respectively; while, in prostate cancer cell lines, it inhibits cancer cell growth with IC50 values ranging from 0.5 to 2.5 μM.

Reference

Michael T Buckley, Joanne Yoon, Herman Yee, Luis Chiriboga, Leonard Liebes, Gulshan Ara, Xiaozhong Qian, Dean F Bajorin, Tung-Tien Sun, Xue-Ru Wu and Iman Osman. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. Journal of Translational Medicine 2007; 5:49

Giovanni Luca Gravina, Francesco Marampon, Ilaria Giusti, Eleonora Carosa, Stefania Di Sante, Enrico Ricevuto, Vincenza Dolo, Vincenzo Tombolini, Emmanuele A Jannini and Claudio Festuccia. Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models. International Journal of Oncology 40: 711-720, 2012

Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.

文献引用

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. Hai Y, Christianson DW. "Histone deacetylase 6 structure and molecular basis of catalysis and inhibition." Nat Chem Biol. 2016 Jul 25. PMID:27454933

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt318.35
Cas No.414864-00-9
FormulaC15H14N2O4S
SynonymsPXD-101, PXD 101, PX105684, PX-105684
Solubility≥15.92 mg/mL in DMSO, ≥44.1 mg/mL in EtOH with ultrasonic, <2.33 mg/mL in H2O
Chemical Name(E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO
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]:

抑制活性

对于活性测定,反应在总体积为150 μl的含有2 μl细胞提取物和2 μl PXD101的缓冲液中进行,缓冲液为含30%甘油的60 mMTris(pH7.4)。通过加入2 μl [3H]标记的底物开始反应,底物对应于乙酰化组蛋白H4的20个NH2末端残基肽。将样品在37℃下孵育45分钟,通过加入终浓度为0.72 M的HCl和0.12 M的乙酸终止反应。将释放的[3H]乙酸酯提取到750 μl乙酸乙酯中,并将样品在12,000×g离心5分钟。将上层相(600 μl)转移到3 ml闪烁液中并计数。

细胞实验 [1]:

细胞系

人膀胱癌细胞系5637、T24、J82和RT4。

溶解方法

该化合物在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

1-5 μM,48 h

实验结果

在人膀胱癌细胞系中,belinostat(PXD101)以剂量依赖性方式抑制细胞增殖,在5637、T24、J82和RT4细胞系中的IC50值分别为1.0、3.5、6.0和10.0 μM。在5637、T24、J82和RT4细胞系中,Belinostat(PXD101)(5 μM)分别减少71%、51%、41%和23%的细胞生长和增殖。此外,belinostat减少S期的细胞,增加G0-G1期的细胞。

动物实验[2]:

动物模型

UPII-Ha-ras转基因小鼠

剂量

100 mg/kg,每周5天,持续3周,腹腔注射

溶解方法

溶于L-精氨酸中,终浓度为20 mg/ml。

实验结果

在UPII-Ha-ras转基因小鼠中,belinostat将雄性和雌性转基因小鼠表达Ras的膀胱的重量分别降低50%和36%。Belinostat抑制膀胱疾病的进展。通过评价重量,Belinostat没有显示出可测量的毒性作用。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Plumb JA, Finn PW, Williams RJ, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther, 2003, 2(8): 721-728.

[2]. Buckley MT, Yoon J, Yee H, et al. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. J Transl Med, 2007, 5: 49.

生物活性

描述 Belinostat (PXD101)是一种新型的pan-HDAC抑制剂,IC50值为27 nM。
靶点 pan-HDAC          
IC50 27 nM          

质量控制

化学结构

Belinostat (PXD101)

相关生物数据

Belinostat (PXD101)

相关生物数据

Belinostat (PXD101)