ML241 hydrochloride
目录号 : GC13656
ML241 hydrochloride 是一种有效的 p97 抑制剂，抑制 p97 ATPase，IC50 值为 100 nM。
Cas No.:2070015-13-1
Sample solution is provided at 25 µL, 10mM.
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IC50: 100 nM
ML241 is identified as a p97 ATPase inhibitor.
The hexameric p97 protein belongs to the type II AAA (ATPase associated with diverse cellular activities) ATPase protein family and is conserved across all eukaryotes and is essential for life
p97 protein, a member of the type II AAA ATPase protein family, is reported to be conservative for nealy all eukaryotes. p97 is also known as valosin-containing protein and Cdc48p in mammals and yeast, respectively, playing key roles in various cellular processes, such as cell division, homotypic fusion of endoplasmic reticulum and Golgi membranes, as well as autophagosome maturations.
In vitro: Both ML241 and its analog ML240 were found to be able to inhibit the degradation of proteasome substrate in a p97-dependent but not a p97-independent manner. ML241 and ML240 could also impaire the endoplasmic-reticulum (ER) associated degradation pathway. ML240 was able to stimulate accumulation of LC3-II potently, inhibit cancer cell growth, and also mobilize the executioner caspases 3 and 7 rapidly, but ML241 was not able to. Further investigation showed that ML240 had broad antiproliferative activity to the NCI-60 panel of cancer cell lines, but lower activity to normal cells. In addition, ML240 could synergize with proteasome inhibitor to inhibit the growth of various colon cancer cell lines. Moreover, both ML241 and ML240 had low off-target activity toward a panel of protein kinases as well as central nervous system targets [1].
In vivo: Currently, there is no animal in vivo data reported.
Clinical trial: Up to now, ML241 is still in the preclinical development stage.
Reference:
[1] Chou TF,Li K,Frankowski KJ,Schoenen FJ,Deshaies RJ. Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase. ChemMedChem.2013 Feb;8(2):297-312.
Cell experiment: | HeLa cells stably expressing ODD-luciferase are seeded onto a 96-well white solid bottom plate (5000 cells/well) and cells are grown for 16 h. Cells are treated with DMEM containing MG132 (4 μM) for 1h and washed with 100 μL PBS twice. DMEM containing 2.5% FBS, cycloheximide (50 μg/mL) and ML241 are added into the well. Four 96-well plates are prepared and one of the plates is taken out from incubator at each time point (70, 90, 120, or 150 min). Luciferin (50 μL of 1 mg/mL in PBS) is added into each well containing 50 μL of medium and incubated at room temperature with shaking at 500 rpm for 5 min. Luminescence intensity is determined with 0.1 ms integration time on the Synergy HT Microplate Reader[2]. |
References: [1]. Chou TF, et al. Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase. ChemMedChem. 2013 Feb;8(2):297-312. | |
| Cas No. | 2070015-13-1 | SDF | |
| 化学名 | 2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine hydrochlorid | ||
| Canonical SMILES | C1(CNC2=NC(N3CCOC4=CC=CC=C43)=NC5=C2CCCC5)=CC=CC=C1.Cl | ||
| 分子式 | C23H25ClN4O | 分子量 | 408.92 |
| 溶解度 | ≥ 40.9mg/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 | 2.4455 mL | 12.2273 mL | 24.4547 mL |
| 5 mM | 0.4891 mL | 2.4455 mL | 4.8909 mL |
| 10 mM | 0.2445 mL | 1.2227 mL | 2.4455 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet