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SGC 0946

现货
Catalog No.
A4167
高效的DOT1L选择性抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,200.00
现货
10mg
¥ 1,800.00
现货

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Background

SGC 0946 is a potent small-molecule inhibitor of protein methyltransferase (PMT) DOT1L, a unique protein lysine methyltransferase (PKMT) catalyzing the methylation of histone H3 on Lysine 79 (H3K79), with the half maximal inhibition concentration IC50 value of 0.3 nM [1].

As a brominated analogue of EPZ004777, SGC 0946 exhibits substantially increased cellular inhibitory potency than its predecessor, where SGC 0946 reduces the methylation of H3K79 in both MCF10A (IC50: 8.8 nM) and A431 (IC50: 2.65 nM) cells compared with EPZ004777 (IC50: 84 nM and 264 nM respectively). This greatly increased cellular inhibitory potency of SGC 0946 can be attributed to lower off-rate and to improved cell permeability [1].

Reference

References:
[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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt618.57
Cas No.1561178-17-3
FormulaC28H40BrN7O4
Solubility≥30.95 mg/mL in DMSO, ≥97.6 mg/mL in EtOH with ultrasonic, <2.3 mg/mL in H2O
SDFDownload SDF
Canonical SMILESCC(C)(C)C1=CC=C(NC(NCCCN(C[C@@H]2[C@@H](O)[C@@H](O)[C@H](N3C4=NC=NC(N)=C4C(Br)=C3)O2)C(C)C)=O)C=C1
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

Molm13白血病细胞以及A431细胞

溶解方法

在DMSO中的溶解度> 31 mg/ml。为了获得更高浓度,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

0-10 μM

应用

在含有MLL/AF9易位的Molm13白血病细胞中,SGC0946能够时间以及浓度依赖性地降低H3K79me2水平。通过自动荧光显微镜定量分析MCF10A细胞中H3K79me2水平,研究发现与EPZ004777((IC50 84±20 nM)相比,SGC0946(IC50 8.8±1.6 nM)能够极大提高对DOT1L的抑制作用。相似的现象也在A431细胞系中观察到,SGC0946 和 EPZ004777的IC50值分别为2.65 nM 和264 nM。

References:

[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.

生物活性

Description SGC 0946是一种有效的DOT1L甲基转移酶抑制剂,IC50值为0.3 nM。
靶点 DOT1L          
IC50 0.3 nM          

质量控制

化学结构

SGC 0946