切换导航

AGI-5198

现货
Catalog No.
A4339
IDH1 R132突变抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
现货
5mg
¥ 1,200.00
现货
25mg
¥ 3,800.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

AGI-5198 is a selective R132H-IDH1 inhibitor which is identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). It is also induced the expression of zinc finger and BTB domain–containing protein 16 (ZBTB16), known as promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor protein which is located on chromosome 11q23 and has been shown to promote glial differentiation in the central nervous system. AGI-5198 is also able to induce the expression of genes and cell markers associated with glial-specific differentiation in glioma cell, the expression of differentiation-associated genes, reduce H3K9 trimethylaytion, and cause tumor growth inhibition.

Reference

Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013)

Francine E Garrett-Bakelman, Ari M Melnick. Differentiation therapy for IDH1/2 mutant malignancies. Cell Research (2013) 23:975–977.

文献引用

1. Yamashita AS, da Costa Rosa M, Borodovsky A, et al."Demethylation and epigenetic modification with 5-Azacytidine reduces IDH1 mutant glioma growth in combination with Temozolomide." Neuro Oncol. 2018 Sep 3. PMID:30184215

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt462.56
Cas No.1355326-35-0
FormulaC27H31FN4O2
SynonymsAGI5198, AGI 5198
Solubility≥23.15 mg/mL in DMSO, ≥18.17 mg/mL in EtOH with ultrasonic and warming, <2.3 mg/mL in H2O
Chemical NameN-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide
SDFDownload SDF
Canonical SMILESCC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C
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

具有内源性杂合R132H-IDH1突变的TS603神经胶质瘤细胞

溶解方法

在DMSO中的溶解度>23.2mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

20-3000 nM; 2天

应用

在R132H-IDH1突变体TS603神经胶质瘤细胞中,AGI-5198抑制R-2HG产生并损害IDH1突变体TS603神经胶质瘤细胞的软琼脂集落形成。

动物实验[1]:

动物模型

建立R132H-IDH1胶质瘤异种移植物的小鼠

剂量

450 mg/kg; 口服; 3周,每天给药

应用

在建立R132H-IDH1胶质瘤异种移植物的小鼠中,AGI-5198(450mg / kg)引起50-60%的生长抑制。AGI-5198耐受良好,无任何毒性迹象。AGI-5198的生长抑制作用主要是由于损伤肿瘤细胞增殖,而不是诱导凋亡性细胞死亡。

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] Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013).

生物活性

描述 AGI-5198是第一个高效的和选择性的IDH1 R132H/R132C突变抑制剂,IC50值分别为0.07 μM/0.16 μM。
靶点 R132H-IDH1 R132C-IDH1        
IC50 0.07 μM 0.16 μM        

质量控制

化学结构

AGI-5198

相关生物数据

AGI-5198

相关生物数据

AGI-5198