AGI-5198
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AGI-5198是一种选择性的R132H-IDH1抑制剂，通过高通量筛选的方式鉴定到。AGI-5198能够以剂量依赖的方式阻断突变酶mIDH1产生R-2-羟基戊二酸。AGI-5198也诱导包含锌指和BTB结构域的蛋白16（ZBTB16），即早幼粒白血病锌指蛋白（PLZF）的表达。PLZF是一种转录阻遏蛋白，位于染色体11q23，能够促进中枢神经系统中胶质细胞分化。AGI-5198也能够诱导神经胶质瘤细胞中与神经胶质特异性分化相关的基因和细胞标志物的表达，诱导分化相关基因的表达，减少H3K9三甲基化，引起肿瘤生长抑制。
参考文献：
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.
- 1. Shuchen Chen, Honglin Zhu, et al. "Molecular and clinical characteristics of IDH mutations in Chinese NSCLC patients and potential treatment strategies." Cancer Med. 2022 May 8. PMID: 35526267
- 2. Yamashita AS, da Costa Rosa M, 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 462.56 |
| Cas No. | 1355326-35-0 |
| Formula | C27H31FN4O2 |
| Synonyms | AGI5198, AGI 5198 |
| Solubility | ≥23.15 mg/mL in DMSO; insoluble in H2O; ≥18.17 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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). |
|
| 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 | ||||
质量控制和MSDS
- 批次:
化学结构
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