L189
目录号 : GC12131
A DNA ligase inhibitor
Cas No.:64232-83-3
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]: | |
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Cell lines |
Human breast epithelial MCF10A cells, human colon cancer HCT116 cells, human cervical cancer HeLa cells, and human breast cancer MCF7 cells. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0~50 µmol/L for 6 days |
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Applications |
In a concentration-dependent manner, L189 (0~50 µmol/L) reduced the proliferation and/or viability of a normal breast epithelial cell line MCF10A and the cancer cell lines MCF7, HeLa, and HCT116 established from breast, cervical, and colon cancers, respectively. In colony-forming assays, L189 was cytotoxic. L189 also increase the rate of killed cells in cancer cell lines, especially HCT116 colon cancer cell line and other cancer cell lines by ionizing radiation. But L189 did not increase the rate of killed cells in the normal cell line. |
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References: [1] Christian Jekimovs, Emma Bolderson, Amila Suraweera, et al. Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising. Frontiers in Oncology, 2014, 4: Article 86. | |
The chemical structure of L189 had been shown [1]. Three distinct chemical steps are involved in the formation of a new phosphodiester bond in DNA: (1) enzyme adenylylation, (2) adenylyl transfer to DNA, and (3) nick sealing [2]. L189 preferentially inhibits the second step [1]. L189 showed no inhibition even at a concentration of 100 μM to T4 DNA ligase. IC50 values for L189 to inhibit human DNA ligases I, III and IV are 5 ± 2 µM, 9 ± 2 µM and 5 ± 2 µM, respectively [1].
DNA ligase I catalyzes the ligation of single-strand breaks to complete DNA replication and repair. DNA ligase III is required for mitochondrial DNA replication and repair. DNA ligase IV is specialized for repair of nuclear double-strand breaks and is required for nonhomologous end joining and V (D) J recombination [2].
In a concentration-dependent manner, L189 reduced the viability and/or proliferation of a normal breast epithelial cell line MCF10A and the cancer cell lines HeLa, MCF7 and HCT116 established from cervical, breast and colon cancers, respectively. L189 also increase the rate of killed cells in cancer cell lines, especially HCT116 colon cancer cell lines and other cancer cell lines by ionizing radiation. But L189 did not increase the rate of killed cells in the normal cell line [1].
In vivo data and clinical trials are not yet available [3].
References:
[1]. Xi Chen, Shijun Zhong, Xiao Zhu, et al. Rational Design of Human DNA Ligase Inhibitors that Target Cellular DNA Replication and Repair. Cancer Res., 2008, 68(9): 3169-3177.
[2]. Mark R. Taylor, John A. Conrad, Daniel Wahl, et al. Kinetic Mechanism of Human DNA Ligase I Reveals Magnesium-dependent Changes in the Rate-limiting Step That Compromise Ligation Efficiency. Journal of Biological Chemistry, 2011, 286(26): 23054-23062.
[3]. Christian Jekimovs, Emma Bolderson, Amila Suraweera, et al. Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising. Frontiers in Oncology, 2014, 4: Article 86.
| Cas No. | 64232-83-3 | SDF | |
| 化学名 | (Z)-6-amino-5-(benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one | ||
| Canonical SMILES | S=C(NC1=O)NC(N)=C1/N=C\C2=CC=CC=C2 | ||
| 分子式 | C11H10N4OS | 分子量 | 246.29 |
| 溶解度 | ≥ 62.5mg/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 | 4.0603 mL | 20.3013 mL | 40.6025 mL |
| 5 mM | 0.8121 mL | 4.0603 mL | 8.1205 mL |
| 10 mM | 0.406 mL | 2.0301 mL | 4.0603 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。