SCR7
目录号 : GC12106
SCR7是一种DNA连接酶IV的小分子抑制剂 ，通过结合连接酶IV的DNA结合域（DBD）来抑制非同源末端连接（NHEJ）途径 。
Cas No.:1533426-72-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | A549 |
Preparation Method | A549 cells were treated with an increasing concentration of SCR7 (10, 50, 100, and 250µM) for 48h. Cell proliferation was then evaluated by MTT assay. The medium was then changed with MTT solution (0.5mg/ml) in DMEM or RPMI without phenol red and FBS; cells were incubated at 37°C for 30min and violet precipitate was dissolved with isopropanol. Absorbance at 550nm was measured through a Plate reader. |
Reaction Conditions | 10, 50, 100, and 250µM, 48h |
Applications | SCR7 can induced cytotoxicity in A549 cells. |
| Animal experiment [1]: | |
Animal models | BALB/c mice bearing EAC tumors |
Preparation Method | Mice bearing EAC tumors were treated with SCR7 (10mg/kg，six doses). Ki67 (a cell proliferation marker), p21 (cell cycle regulator) and apoptotic markers such as BID and Caspase 3 were measured in treated sections by immunohistochemistry. |
Dosage form | 10mg/kg, every alternate day for six doses, i.p. |
Applications | Accumulation of DSBs upon SCR7 treatment activates p53-mediated intrinsic pathway of apoptosis in BALB/c mice. |
References: | |
SCR7 is a small molecule inhibitor of DNA Ligase IV [1] [2], which inhibits the non-homologous end-joining (NHEJ) pathway by binding to the DNA binding domain (DBD) of Ligase IV [3]. SCR7 is commonly used in cancer therapeutic research [4] and serves as a valuable tool for improving the efficiency of genome editing [5].
SCR7 exhibits concentration- and time-dependent cytotoxicity in DLBCL cells (SUDHL8) via both extrinsic and intrinsic apoptosis pathways. In SUDHL8 cells, treatment with SCR7 at 100 and 250µM for 48 and 72 hours increases mitochondrial membrane potential, causes translocation of phosphatidylserine to the cell surface, and raises the expression of double-strand break repair proteins and apoptotic markers [6].
SCR7 (10mg/kg, every alternate day for six doses, i.p.) treatment can significantly enhance the the effect of radiation in mice with Dalton's lymphoma (DLA) liquid tumors. The combination of SCR7 and ionizing radiation (IR) can markedly reduce tumor growth and improve the survival rate of tumor-bearing mice [7].
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]. Gkotzamanidou M, Terpos E, Bamia C, et al. DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7. Blood. 2016 Sep 1;128(9):1214-25. doi: 10.1182/blood-2016-01-691618. Epub 2016 Jul 21. PMID: 27443291; PMCID: PMC5524533.
[3]. Manjunath M, Choudhary B, Raghavan SC. SCR7, a potent cancer therapeutic agent and a biochemical inhibitor of nonhomologous DNA end-joining. Cancer Rep (Hoboken). 2021 Jun;4(3):e1341. doi: 10.1002/cnr2.1341. Epub 2021 Jan 26.
[4]. Vartak SV, Swarup HA, Gopalakrishnan V, et al. Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner. FEBS J. 2018 Nov;285(21):3959-3976. doi: 10.1111/febs.14661. Epub 2018 Oct 8. PMID: 30230716.
[5]. Hu Z, Shi Z, Guo X, Jiang B, Wang G, Luo D, Chen Y, Zhu YS. Ligase IV inhibitor SCR7 enhances gene editing directed by CRISPR-Cas9 and ssODN in human cancer cells. Cell Biosci. 2018 Feb 19;8:12. doi: 10.1186/s13578-018-0200-z. PMID: 29468011; PMCID: PMC5819182.
[6]. Gopalakrishnan V, Radha G, Raghavan SC, et al. Inhibitor of nonhomologous end joining can inhibit proliferation of diffuse large B-Cell lymphoma cells and potentiate the effect of ionization radiation. J Radiat Cancer Res 2018;9:93-101. DOI: 10.4103/jrcr.jrcr_9_18
[7]. Gopalakrishnan V, Sharma S, Ray U, et al. SCR7, an inhibitor of NHEJ can sensitize tumor cells to ionization radiation. Mol Carcinog. 2021 Sep;60(9):627-643. doi: 10.1002/mc.23329. Epub 2021 Jun 30.
SCR7是一种DNA连接酶IV的小分子抑制剂 [1] [2] ，通过结合连接酶IV的DNA结合域（DBD）来抑制非同源末端连接（NHEJ）途径 [3] 。SCR7常用于癌症治疗研究 [4] ，并且是提高基因组编辑效率的重要工具 [5] 。
SCR7在DLBCL细胞（SUDHL8）中表现出浓度和时间依赖的细胞毒性，作用途径包括外源性和内源性凋亡。SUDHL8细胞经100和250µM的SCR7处理48和72小时后，线粒体膜电位增加，磷脂酰丝氨酸转移到细胞表面，双链断裂修复蛋白和凋亡标志物的表达增加 [6] 。
SCR7（10mg/kg，每隔一天一次，共六次，腹腔注射）处理能够显著增强辐射对患有道尔顿淋巴瘤（DLA）液体肿瘤小鼠的效果。SCR7与电离辐射（IR）的联合使用可以显著减少肿瘤生长并提高带瘤小鼠的存活率 [7] 。
| Cas No. | 1533426-72-0 | SDF | |
| 化学名 | 5,6-bis((E)-benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one | ||
| Canonical SMILES | S=C(NC(/N=C/C1=CC=CC=C1)=C2/N=C/C3=CC=CC=C3)NC2=O | ||
| 分子式 | C18H14N4OS | 分子量 | 334.39 |
| 溶解度 | ≥ 16.7195mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9905 mL | 14.9526 mL | 29.9052 mL |
| 5 mM | 0.5981 mL | 2.9905 mL | 5.981 mL |
| 10 mM | 0.2991 mL | 1.4953 mL | 2.9905 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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