切换导航

UNC0638

现货
Catalog No.
A1914
有效的G9a/GLP HMTase选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 780.00
现货
5mg
¥ 720.00
现货
10mg
¥ 980.00
现货
50mg
¥ 3,040.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

UNC0638 is a potent and selective inhibitor of G9a and GLP with IC50 values of < 15 nM and 19 ± 1 nM, respectively [1].

GLP forms a heterodimer with G9a. Both G9a and GLP can mono- and dimethylate histone H3 Lys9 (H3K9), and dimethylate Lys373 of p53 and hence inactivate the transcriptional activity of p53 [1].

UNC0638 showed balanced physicochemical properties and potency aiding cell penetration in vitro, had high potency in cellular assays. It was much less toxic than BIX01294 to cells. In MDA-MB-231 cells, in a concentration-dependent manner, exposure to UNC0638 for 48 h reduced H3K9me2 levels with an IC50 value of 81 ± 9 nM (n= 3), which showed considerably higher potency than BIX01294 (IC50= 500 ± 43 nM (n= 3)). In reducing H3K9me2 levels, UNC0638 was of greater maximum effect than BIX01294. This effect is close, but not equal, to the effect on the double knockdown of G9a and GLP via shRNA [1].

In 6-week-old male athymic nude mice subcutaneously inoculated with BON cells, UNC0638 decreased H3K9me2 level [2]. In organotypic cochlear cultures, rapid increase of H3K9me2 upon the damage of hair cells was observed. Both ex vivo and in vivo, UNC0638 effectively prevented aminoglycosides-induced hair cell damage [3].

References:
[1].  Vedadi M., Barsyte-Lovejoy D., Liu F., et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nature Chemical Biology, 2011, 7:566-574.
[2].  Kim J.T., Li J., Jang E.R., et al. Deregulation of Wnt/β-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors. Clin. Carcinogenesis, 2013, 00(00):1-9.
[3].  Yu H., Lin Q., Wang Y., et al. Inhibition of H3K9 methyltransferases G9a/GLP prevents ototoxicity and ongoing hair cell death. Cell Death and Disease, 2013, 4:e506.

文献引用

1. Liu M, Thomas SL, et al. "Dual Inhibition of DNA and Histone Methyltransferases Increases Viral Mimicry in Ovarian Cancer Cells." Cancer Res. 2018 Oct 15;78(20):5754-5766. PMID:30185548

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt509.72
Cas No.1255580-76-7
FormulaC30H47N5O2
Solubility≥25.5mg/mL in DMSO
Chemical Name2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine
SDFDownload SDF
Canonical SMILESCC(C)N1CCC(CC1)NC2=NC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)C5CCCCC5
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

细胞实验 [1]:

细胞系

MDA-MB-231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。原液在-20℃下可放置数月。

反应条件

80, 250, 500 nM;1 ~ 4 天

试验结果

在MDA-MB-231细胞中,UNC0638于48小时内呈浓度依赖性地降低H3K9me2水平,其IC50值为81 ± 9 nM。在80 nM(IC50)、250 nM(IC90)和500 nM(2 × IC90)这3个浓度水平下,UNC0638自第1天到第4天逐步降低H3K9me2的细胞水平。给予250 nM和500 nM UNC0638,持续4天,能将H3K9me2水平降至或接近其在G9a和GLP敲除细胞中的水平。UNC0638具有长效作用。给予UNC0638,持续2天,再清洗细胞,然后将其置于无抑制剂的培养液中孵育2天。结果表明,于实验的第3天和第4天,细胞内的H3K9me2水平仍然较低。

动物实验 [2]:

动物模型

瑞士白化小鼠

给药剂量

5 mg/kg;腹腔注射.

实验结果

由于UNC0638的药物代谢动力学参数较差,UNC0638不适用于动物实验。

其他注意事项

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]. Vedadi M., Barsyte-Lovejoy D., Liu F., et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nature Chemical Biology, 2011, 7:566-574.

[2]. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42.

生物活性

描述 UNC0638是一种有效的G9a/GLP HMTase选择性抑制剂,其IC50值分别为< 15 nM和19 nM。
靶点 G9a GLP        
IC50 < 15 nM 19 nM        

质量控制

化学结构

UNC0638

相关生物数据

UNC0638