SCR7 pyrazine

SCR7 pyrazine用途

SCR7 pyrazine 是一种 DNA 连接酶 IV (DNA ligase IV) 抑制剂,它以连接酶 IV 依赖的方式阻断非同源末端连接 (NHEJ)。SCR7 pyrazine 也是一种 CRISPR/Cas9 的增强子,可提高 Cas9 介导的同源性定向修复 (HDR) 的效率。SCR7 pyrazine 诱导细胞凋亡 (apoptosis) 并具有抗癌活性。

SCR7 pyrazine名称

[ CAS 号 ]:
14892-97-8

[ 中文名 ]:
SCR7吡嗪

[ 英文名 ]:
SCR7 pyrazine

[英文别名 ]:

4-Oxo-6,7-diphenyl-2-thioxotetrahydropteridin
6,7-diphenyl-2-thiolumazine
2-Thioxo-4-oxo-6,7-diphenyl-1H,3H-pteridin
6,7-Diphenyl-2-thioxo-2,3-dihydro-1H-pteridin-4-on
SCR7 pyrazine

SCR7 pyrazine生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成

信号通路 >> 细胞周期/DNA损伤 >> CRISPR/Cas9

[ 靶点 ]

DNA Ligase IV[1] CRISPR/Cas9[2]

[体外研究]

SCR7吡嗪(20-100μM；24小时；MCF7细胞)处理干扰细胞内的NHEJ,导致未修复的双链断裂(DSB)累积[1]。SCR7吡嗪处理显示细胞增殖的IC50值呈剂量依赖性降低,MCF7、A549、HeLa、T47D、A2780、HT1080和Nalm6细胞的IC50值分别为40μM、34μM、44μM、8.5μM、120μM、10μM和50μM[1]。在MCF7细胞中,SCR7-吡嗪(20,40μM)处理增加了ATM的磷酸化,激活了p53,降低了MDM2和BCL2,从而激活了促凋亡蛋白PUMA和BAX。MCL1、PARP1、caspase3和caspase9裂解的短片段呈剂量依赖性上调[1]。westernblot分析[1]细胞系：MCF7细胞浓度：20μM,40μM,100μM孵育时间：24小时结果：gH2AX病灶和蛋白水平升高。

[体内研究]

SCR7吡嗪(10mg/kg；腹腔注射；6个剂量；BALB/c小鼠)治疗显著减少乳腺癌诱发的肿瘤并延长寿命[1]。动物模型：BALB/c小鼠注射乳腺癌细胞[1]剂量：10mg/kg给药：腹腔注射；隔日(0、2、4、6、8、10)结果：乳腺癌诱发的肿瘤明显减少,寿命延长。

[参考文献]

[1]. Srivastava M, 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.

[2]. Lin C, et al. Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1 Virus in Human Cells. Sci Rep. 2016 Oct 7;6:34531.

SCR7 pyrazine物理化学性质

[ 熔点 ]:
209 °C

[ 分子式 ]:
C₁₈H₁₂N₄OS

[ 分子量 ]:
332.37900

[ 精确质量 ]:
332.07300

[ PSA ]:
110.59000

[ LogP ]:
3.74810

[ 外观性状 ]:
固体;White to Yellow to Green powder to crystal

[ 储存条件 ]:
0-10°C;避免加热

SCR7 pyrazine安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 危险品运输编码 ]:
NONH for all modes of transport

SCR7 pyrazine文献

Increasing the efficiency of CRISPR/Cas9-mediated precise genome editing in rats by inhibiting NHEJ and using Cas9 protein.

.PubMed ID

Precise modifications such as site mutation, codon replacement, insertion or precise targeted deletion are needed for studies of accurate gene function. The CRISPR/Cas9 system has been proved as a pow...

Enrichment of G2/M cell cycle phase in human pluripotent stem cells enhances HDR-mediated gene repair with customizable endonucleases.

Sci. Rep. 6 , 21264, (2016)

Efficient gene editing is essential to fully utilize human pluripotent stem cells (hPSCs) in regenerative medicine. Custom endonuclease-based gene targeting involves two mechanisms of DNA repair: homo...

Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining.

Nat. Biotechnol. 33(5) , 538-42, (2015)

Methods to introduce targeted double-strand breaks (DSBs) into DNA enable precise genome editing by increasing the rate at which externally supplied DNA fragments are incorporated into the genome thro...

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