EPZ004777
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.
EPZ004777是一种特异性的H3K79甲基转移酶DOT1L小分子抑制剂,在放射性同位素试验中可有效抑制DOT1L,半数最大抑制浓度IC50值为400 pM,也可选择性杀死多种MLL重排的白血病细胞,包括一种MLL-AF4白血病细胞系MV4-11和一种MLL-AF9白血病细胞系MOLM13[1 & 2]。
EPZ004777也可以剂量依赖的方式选择性地抑制MLL-AF10和CALM-AF10转化细胞(IC50:0.1 μM到1 μM),期间两个标记白血病基因(Hoxa9和Meis1)的mRNA表达水平被EPZ004777以浓度依赖的方式抑制[2]。
参考文献:
[1] Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288. doi: 10.1038/ncomms2304.
[2] Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C, Olhava EJ, Daigle SR, Richon VM, Pollock RM, Armstrong SA. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2013 Apr;27(4):813-22. doi: 10.1038/leu.2012.327. Epub 2012 Nov 9.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 539.67 |
Cas No. | 1338466-77-5 |
Formula | C28H41N7O4 |
Solubility | ≥27 mg/mL in DMSO; insoluble in H2O; ≥94.6 mg/mL in EtOH with ultrasonic |
Chemical Name | 1-[3-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)urea |
SDF | |
Canonical SMILES | CC(C)N(CCCNC(=O)NC1=CC=C(C=C1)C(C)(C)C)CC2C(C(C(O2)N3C=CC4=C3N=CN=C4N)O)O |
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 |
人类白血病细胞系MV4-11和Molm13细胞 |
溶解方法 |
在DMSO中的溶解度大于10 mM。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 |
96 h,10 μM |
应用 |
EPZ004777是一个特异的DOT1L强效抑制剂,在放射性核素均相实验中的IC50为400 pM。它可以选择性的杀死含有和致癌MLL融合蛋白互作而定位异常的DOT1L的混合系白血病细胞。 |
动物实验[2]: | |
动物模型 |
8周龄的C57BL/6小鼠 |
剂量 |
向小鼠体内植入对照(15%乙醇,50% PEG300,35%水)或150 mg/ml EPZ004777的渗透泵,一周后更换渗透泵,继续给药一周。 |
应用 |
EPZ004777在小鼠中耐受性良好,没有明显的毒性。在小鼠MLL白血病移植瘤模型中,EPZ004777具有抗肿瘤和药效作用。 |
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]. Yu W, Chory E J, Wernimont A K, et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors[J]. Nature communications, 2012, 3: 1288. [2]. Daigle S R, Olhava E J, Therkelsen C A, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor[J]. Cancer cell, 2011, 20(1): 53-65. |
质量控制和MSDS
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