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JIB-04

现货
Catalog No.
B1579
Jumonji组蛋白去甲基化酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 900.00
现货
20mg
¥ 1,380.00
现货
50mg
¥ 2,590.00
现货

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Background

JIB-04 is a small molecule inhibitor of Jumonji histone demethylase with IC50 values of [1].

JIB-04 is a pyridine hydrazone. It is a pan -selective inhibitor of Jumonji histone demethylases. In a sensitive ELISA assay, JIB-04 inhibits JARID1A, JMJD2A, JMJD2B, JMJD2C, JMJD2E and JMJD3 with IC50 values of 230nM, 445nM, 435nM, 1100nM, 340nM and 855nM, respectively. Among the JMJD2 (KDM4) subfamily, JMJD2D has highest sensitivity. JIB-04 inhibits Jumonji demethylases in a unique manner. It is found not to be a competitive inhibitor of α-ketoglutarate in the competition assay [1].

JIB-04 shows consistently selective for cancer cells over normal cells. It has efficacy in cultured lung and prostate cancer lines with IC50 values as low as 10nM. JIB-04 is also effective in controlling lung cancer growth in animals. It significantly suppresses tumor growth of H358 and A549 lung cancer cell xenografts in mice with IC50 values of 100nM and 250nM, respectively. Furthermore, the anti-proliferation activity of JIB-04 results in a reduction in cancer-induced death rates in mice [1].

References:
[1] Wang L, Chang J, Varghese D, Dellinger M, Kumar S, Best AM, Ruiz J, Bruick R, Peña-Llopis S, Xu J, Babinski DJ, Frantz DE, Brekken RA, Quinn AM, Simeonov A, Easmon J, Martinez ED. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035.

文献引用

1. Parrish JK, McCann TS, et al. "The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell proliferation and survival, and reduced tumor growth." Oncotarget. 2018 Sep 4;9(69):33110-33123. PMID:30237855

Chemical Properties

StorageStore at -20°C
M.Wt308.76
Cas No.199596-05-9
FormulaC17H13ClN4
Solubility≥14.2mg/mL in DMSO
Chemical Name5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)C(=NNC2=NC=C(C=C2)Cl)C3=CC=CC=N3
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

人肺癌细胞系(LCa);HBECs,前列腺癌(PCa);原发性前列腺基质(PrSC)和前列腺上皮细胞(PrEC)

制备方法

溶解度有限,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

4 days

实验结果

相对于正常细胞HBEC和PrSCs/PrEC,JIB-04对肺癌和前列腺癌细胞系表现出选择性,IC50低至10 nM。此外,0.1-2 μM的JIB-04E-异构体降低总H3K9me3去甲基化酶的活性,表明在类似于体外抑制单个纯化酶的浓度下,JIB-04抑制细胞中的H3K9me3去甲基化酶。

动物实验: [1]

动物模型

H358和A549肺癌异种移植物小鼠

给药剂量

在H358异种移植物中以110 mg/kg芝麻油,每周通过IP注射给药2-3次;在A549异种移植物中,Cremophor EL中以55 mg/kg进行饲喂。

实验结果

与载体处理组相比,JIB-04显著消除了肿瘤生长的速率,它还显著降低最终肿瘤重量,而不影响总体重或一般健康。此外,JIB-04降低了肿瘤中Jumonji组蛋白去甲基化酶的活性,并延长癌症的存活。

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. Wang L, Chang J, Varghese D et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035.

生物活性

描述 JIB-04是一种广谱的选择性Jumonji组蛋白去甲基化酶抑制剂,作用于JARID1A、JMJD2E、JMJD3、JMJD2A、JMJD2B、JMJD2C和JMJD2D,IC50值分别为230、340、855、445、435、1100和290 nM。
靶点 JARID1A JMJD2D JMJD2E JMJD2B JMJD2A JMJD3
IC50 230 nM 290 nM 340 nM 435 nM 445 nM 855 nM

质量控制

化学结构

JIB-04

相关生物数据

JIB-04