L82-G17
目录号 : GC68436L82-G17 是一种非竞争性 DNA 连接酶 I (Lig I) 选择性抑制剂。L82-G17 抑制连接反应的第三步，即磷酸二酯键的形成。L82-G17 可用作催化活性的探针。
Cas No.:92285-87-5
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
L82-G17 is an uncompetitive DNA ligase I (Lig I)-selective inhibitor. L82-G17 inhibits the third step of the ligation reaction, phosphodiester bond formation. L82-G17can be used as a probe of the catalytic activity[1].
L82-G17 (200 μM, 30 min) has selective uncompetitive inhibitory effect for LigI[1].
L82-G17 (0-100 μM) increases LigI binding to non-ligatable nicked DNA binding[1].
L82-G17 inhibits step 3 of the ligation reaction, phosphodiester bond formation[1].
L82-G17 (0-100 μM) inhibits DNA synthesis, cell viability and s induces DNA damage[1].
Cell Viability Assay[1]
| Cell Line: | HeLa cells |
| Concentration: | 0-30 μM |
| Incubation Time: | 5 days |
| Result: | Reduced cell number by about 70% at 20 μM. |
Cell Proliferation Assay[1]
| Cell Line: | CH12F3 WT and CH12F3δ/δ cells |
| Concentration: | 0-100 μM |
| Incubation Time: | 72 h |
| Result: | Had great effect on the proliferation and survival of the parental CH12F3 cells. |
[1]. Timothy R L Howes, et al. Structure-activity relationships among DNA ligase inhibitors: Characterization of a selective uncompetitive DNA ligase I inhibitor. DNA Repair (Amst). 2017 Dec;60:29-39.
| Cas No. | 92285-87-5 | SDF | Download SDF |
| 分子式 | C11H9ClN4O2 | 分子量 | 264.67 |
| 溶解度 | DMSO : 125 mg/mL (472.29 mM; Need ultrasonic) | 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 | 3.7783 mL | 18.8914 mL | 37.7829 mL |
| 5 mM | 0.7557 mL | 3.7783 mL | 7.5566 mL |
| 10 mM | 0.3778 mL | 1.8891 mL | 3.7783 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。
Structure-activity relationships among DNA ligase inhibitors: Characterization of a selective uncompetitive DNA ligase I inhibitor
DNA Repair (Amst) 2017 Dec;60:29-39.PMID:29078112DOI:PMC5881949
In human cells, there are three genes that encode DNA ligase polypeptides with distinct but overlapping functions. Previously small molecule inhibitors of human DNA ligases were identified using a structure-based approach. Three of these inhibitors, L82, a DNA ligase I (LigI)-selective inhibitor, and L67, an inhibitor of LigI and DNA ligases III (LigIII), and L189, an inhibitor of all three human DNA ligases, have related structures that are composed of two 6-member aromatic rings separated by different linkers. Here we have performed a structure-activity analysis to identify determinants of activity and selectivity. The majority of the LigI-selective inhibitors had a pyridazine ring whereas the LigI/III- and LigIII-selective inhibitors did not. In addition, the aromatic rings in LigI-selective inhibitors had either arylhydrazone or acylhydrazone, but not vinyl linkers. Among the LigI-selective inhibitors, L82-G17 exhibited increased activity against and selectivity for LigI compared with L82. Notably. L82-G17 is an uncompetitive inhibitor of the third step of the ligation reaction, phosphodiester bond formation. Cells expressing LigI were more sensitive to L82-G17 than isogenic LIG1 null cells. Furthermore, cells lacking nuclear LigIIIα, which can substitute for LigI in DNA replication, were also more sensitive to L82-G17 than isogenic parental cells. Together, our results demonstrate that L82-G17 is a LigI-selective inhibitor with utility as a probe of the catalytic activity and cellular functions of LigI and provide a framework for the future design of DNA ligase inhibitors.