M3814 (nedisertib)
(Synonyms: M3814) 目录号 : GC32718
Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with IC50 of < 3 nM.
Cas No.:1637542-33-6
Sample solution is provided at 25 µL, 10mM.
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Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with IC50 of < 3 nM.
M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells leads to an increased number of persistent DSBs.[2]
Inhibition of DNA-PK autophosphorylation in xenograft tumors leads to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiates the antitumor activity of IR and lead to complete tumor regression at nontoxic doses.[2]
[1] Thomas Fuchss, et al. WO2014183850A1. [2] Frank T Zenke, et al. Mol Cancer Ther. 2020 May;19(5):1091-1101.
Animal experiment: | The efficacy of Nedisertib in combination with IR is evaluated in 6 human xenograft models (HCT116, FaDu, NCI-H460, A549, Capan-1, BxPC3) in mice representing 4 different cancer types (colon, head and neck, lung, and pancreas). Tumor cells are injected s.c. into nude mice, and treatment starts when palpable tumors are established (~100 to 200 mm3 ). Nedisertib is given orally at different doses (25 to 300 mg/kg) 10 min prior to IR. IR is applied using a radiation therapy device for small rodents calibrated to deliver 2 Gy. Autophosphorylation of DNA-PK (serine2056 ) in FaDu tumor lysates is measured by immunoassay to assess pharmacological inhibition by Nedisertib[1]. |
References: [1]. L. Damstrup, et al. M3814, a DNA-dependent Protein Kinase Inhibitor (DNA-PKi), Potentiates the Effect of Ionizing Radiation (IR) in Xenotransplanted Tumors in Nude Mice. IJROBP. 2016; 94, 940-941. | |
| Cas No. | 1637542-33-6 | SDF | |
| 别名 | M3814 | ||
| Canonical SMILES | COC1=CC=C([C@@H](O)C2=CC(C3=C(C=CC(N4CCOCC4)=C5)C5=NC=N3)=C(F)C=C2Cl)N=N1 | ||
| 分子式 | C24H21ClFN5O3 | 分子量 | 481.91 |
| 溶解度 | DMSO : 100 mg/mL (207.51 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 2.0751 mL | 10.3754 mL | 20.7508 mL |
| 5 mM | 0.415 mL | 2.0751 mL | 4.1502 mL |
| 10 mM | 0.2075 mL | 1.0375 mL | 2.0751 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet