EPZ5676
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.
EPZ5676是一种有效的DOT1L组蛋白甲基转移酶抑制剂。X射线晶体分析表明,EPZ5676占据S-腺苷甲硫氨酸(SAM)的结合口袋,诱导DOT1L的构象变化,导致SAM疏水口袋以外的氨基酸部分的开放。EPZ5676选择性地抑制DOTIL,IC50值为0.8 nM,比对其它甲基转移酶的选择性高37000倍,包括CARM1、EHMT1/2、EZH1/2、PRMT1/2/5/6/8、SETD7、SMYD2/3和WHSC1/1L1。在EPZ5676用于治疗MLL重排白血病的多个研究中,EPZ5676抑制H3K79的甲基化和MLL融合靶基因的表达,并有效杀死MLL易位的急性白血病细胞系。
参考文献:
Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025.
- 1. Liu L, Zou J, et al. "Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition." FASEB J. 2019 Aug 2:fj201801861R. PMID:31373855
- 2. Kim MS, Cho HI, et al. "JIB-04, A Small Molecule Histone Demethylase Inhibitor, Selectively Targets Colorectal Cancer Stem Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway." Sci Rep. 2018 Apr 26;8(1):6611. PMID:29700375
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 562.71 |
Cas No. | 1380288-87-8 |
Formula | C30H42N8O3 |
Solubility | ≥28.15 mg/mL in DMSO; insoluble in H2O; ≥50.3 mg/mL in EtOH with ultrasonic |
Chemical Name | (2R,3S,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylamino]methyl]oxolane-3,4-diol |
SDF | Download SDF |
Canonical SMILES | CC(C)N(CC1C(C(C(O1)N2C=NC3=C2N=CN=C3N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C |
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。 |
激酶实验 [1]: | |
酶抑制试验 |
将抑制数据拟合到Morrison二次方程,计算EPZ5676酶抑制常数(Ki值)。通过表面等离子共振测定EPZ5676停留时间。EPZ5676停留时间为酶-配体解离速率的倒数,。 |
细胞实验 [1]: | |
细胞系 |
MV4-11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 °C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 °C可放置数月。 |
反应条件 |
0.0005 ~ 10 μM;14天 |
实验结果 |
EPZ5676有效抑制MV4-11细胞增殖,其IC50值为3.5 nM。于EPZ5676治疗后的第4天,EPZ-5676开始显示出抗增殖活性。于EPZ-5676治疗后的第7天,其抗增殖活性最显著。 |
动物实验 [1]: | |
动物模型 |
携带MV4-11异种移植瘤的裸鼠 |
给药剂量 |
35、67或70 mg/kg/day;静脉注射;持续21天 |
实验结果 |
在携带MV4-11异种移植瘤的裸鼠中,EPZ5676使肿瘤完全消退。即使停止给药,其作用仍能持续一段时间。EPZ5676不会引起显著的体重减轻或毒性。 |
其它注意事项 |
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]. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025. |
描述 | EPZ5676是一种有效的和选择性的DOT1L甲基转移酶抑制剂,Ki值为80 pM。 | |||||
靶点 | DOT1L | |||||
IC50 | 80 pM (Ki) |
质量控制和MSDS
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