STL127705
目录号 : GC65249
STL127705 (Compound L) 是一种有效的 Ku 70/80 异二聚体蛋白 Ku 70/80 heterodimer protein 抑制剂，IC50 为 3.5 μM。STL127705 通过抑制 DNA-PKCS 激酶的激活干扰 Ku70/80 与 DNA 的结合。STL127705 显示出抗增殖和抗肿瘤活性。 STL127705 诱导细胞凋亡 (apoptosis) 。
Cas No.:1326852-06-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
STL127705 (Compound L) is a potent Ku 70/80 heterodimer protein inhibitor with an IC50 of 3.5 μM. STL127705 interferes the binding of Ku70/80 to DNA and by inhibits the activation of the DNA-PKCS kinase. STL127705 shows antiproliferative and anticancer activity. STL127705 induces apoptosis[1][2].
STL127705 (Compound L) (0-100 µM) inhibits binding of Ku70/80 to a DNA substrate and inhibits Ku-dependent activation of the DNA-PKCS kinase[1].antiproliferative activity (0-100 µM; 6h) decreases the expression of DNA-PKCS auto-phosphorylation in SF-767 cells[1].STL127705 (0-40 µM; 6h) shows antiproliferative activity in a dose dependent manner[1].TL127705 (1 µM; 48 h) significantly promotes apoptotic when combination with gemcitabine[2].
[1]. Weterings E, et al. A novel small molecule inhibitor of the DNA repair protein Ku70/80. DNA Repair (Amst). 2016 Jul;43:98-106.
[2]. Guo N, et al. Inhibiting nonhomologous end-joining repair would promote the antitumor activity of gemcitabine in nonsmall cell lung cancer cell lines. Anticancer Drugs. 2022 Jun 1;33(5):502-508.
| Cas No. | 1326852-06-5 | SDF | Download SDF |
| 分子式 | C22H20FN5O4 | 分子量 | 437.42 |
| 溶解度 | Water : 100 mg/mL (228.61 mM; Need ultrasonic)|DMSO : 2.4 mg/mL (5.49 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 | 2.2861 mL | 11.4307 mL | 22.8613 mL |
| 5 mM | 0.4572 mL | 2.2861 mL | 4.5723 mL |
| 10 mM | 0.2286 mL | 1.1431 mL | 2.2861 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。
Inhibiting nonhomologous end-joining repair would promote the antitumor activity of gemcitabine in nonsmall cell lung cancer cell lines
Anticancer Drugs 2022 Jun 1;33(5):502-508.PMID:35276695DOI:10.1097/CAD.0000000000001290
Nonsmall cell lung cancer (NSCLC) is a major type of lung cancer. In current study, we aim to evaluate whether the combination of Ku70/80 heterodimer protein inhibitor STL127705 and gemcitabine would be more favorable approach for the treatment of NSCLC compared with monotreatment with gemcitabine. Clongenic survival assay was used to determine the survival and sensitivity to irradiation. H1299 was stained with fluorescein isothiocyanate-Annexin V, and cell apoptosis was measured by flow cytometry. H1299 cells were transfected with nonhomologous end-joining (NHEJ) repair reporter, and stable cell line was selected by puromycin. NHEJ activity was determined based on the intensity of green fluorescent protein. DNA double-strand breaks (DSBs) were determined by the fluorescence intensity of γH2AX using flow cytometry. The mRNA expressions of Ku70 and Ku80 were determined using quantitative real-time PCR. Combination of STL127705 enhanced sensitivity of NSCLC cell lines to irradiation when compared with treatment with gemcitabine alone. However, small cell lung cancer cell line was not affected. H1299 cells treated with STL127705 in combination with gemcitabine showed a significantly increased apoptosis compared with H1299 cells treated with gemcitabine alone. Moreover, STL127705 treatment dramatically reduced NHEJ activity in H1299 cells when compared with gemcitabine single treatment. Increased DSBs were consistently observed in H1299 when treated with the combination of STL127705 and gemcitabine. However, the mRNA levels of Ku70 and Ku80 were upregulated by the combination treatment. It demonstrated that STL127705 enhanced antitumor activity of gemcitabine. Mechanistically, treatment with STL127705 enhanced DNA damage via inhibiting NHEJ pathway, blocking DNA-PK, and forming Ku70/80 heterodimer, eventually leading to tumor cells apoptosis.