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SCR7

现货
Catalog No.
A8705
DNA连接酶IV抑制剂。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
5mg
¥ 700.00
现货
25mg
¥ 2,100.00
现货

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Background

Scr7 is a DNA ligase IV inhibitor, initially identified as an anti-cancer agent [1].
Scr7 targets the DNA binding domain of DNA ligase IV, reducing its affinity for double strand breaks (DSBs) and inhibiting its function. Scr7 also inhibits DNA ligase III (but not DNA ligase I), albeit less efficiently. Cells were treated with doxycycline to induce Cas9 expression, with various concentrations of Scr7 for 24 h. Scr7 maintained cells capable of entering S/G2 phase, which is necessary for HDR. [1] Treatment of mice with Scr7 affects lymphocyte development, as DNA ligase IV plays a key role in the joining of coding ends during V(D)J recombination by means of C-NHEJ16. The defects in lymphocyte development upon Scr7 treatment are transient and reversible, due to the noncovalent mode of binding of Scr7. Scr7 enhanced the frequency of HDR by transiently blocking NHEJ (with the exception of DNA ligase I–dependent alt-NHEJ), resulting in precise genome editing by CRISPR-Cas9 in both cultured cells and in mice. [2]
References:
[1]. Srivastava M, Nambiar M, Sharma S et al. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012 Dec 21;151(7):1474-87. doi: 10.1016/j.cell.2012.11.054.
[2]. Maruyama T, Dougan SK, Truttmann MC et al.Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 Mar 23. doi: 10.1038/nbt.3190. [Epub ahead of print]

文献引用

Chemical Properties

StorageStore at -20°C
M.Wt334.39
Cas No.1533426-72-0
FormulaC18H14N4OS
Solubility≥16.7195mg/mL in DMSO
Chemical Name5,6-bis((E)-benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
SDFDownload SDF
Canonical SMILESS=C(NC(/N=C/C1=CC=CC=C1)=C2/N=C/C3=CC=CC=C3)NC2=O
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

上皮(A549)和黑色素瘤(MelJuSo)细胞系衍生物

制备方法

该化合物在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℃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℃可放置数月。

反应条件

24 小时, 37℃

实验结果

Scr7增加细胞系中插入诱变的效率。在A549细胞中,相较于未处理的对照组,0.01 μM Scr7将靶位点的插入效率提高约三倍。在Scr7处理的MelJuSo细胞中,插入效率也以剂量依赖性方式增强高达19倍。

动物实验: [1]

动物模型

Kell-LPETG小鼠

给药剂量

在原核阶段将CRISPR组分混合物(Cas9 mRNA、sgRNA和靶向模板)和10 mM的Scr7 NHEJ抑制剂(至终浓度为1 mM)注射到细胞质中。将注射的受精卵在2-细胞阶段转移到假孕妇中。

实验结果

共注射Scr7增加了在小鼠胚胎中精确基因组编辑的效率。与未注射Scr7的胚泡相比,使用Scr7共注射的插入效率显著增高(P = 0.0012)。与未注射Scr7的E10胚胎相比,Scr7共注射的E10胚胎中的插入效率也显著增高(P = 0.003)。

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. Maruyama T, Dougan SK, Truttmann MC et al. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 May;33(5):538-42.

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