ML-264
(Synonyms: (2E)-3-(3-氯苯基)-N-[2-[甲基(四氢-1,1-二氧代-2H-噻喃-4-基)氨基]-2-氧代乙基]-2-丙烯酰胺) 目录号 : GC11307
A selective KLF5 inhibitor
Cas No.:1550008-55-3
Sample solution is provided at 25 µL, 10mM.
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ML264, a potent and selective inhibitor of kruppel-like factor 5 (KLF5), inhibits the growth of colorectal cancer. ML264 is chemically stable, unreactive with glutathione, has suitable aqueous solubility, is highly stable to mouse, rat, and human hepatic microsomes, making it a good candidate for in vivo anticancer studies [1].
ML264 inhibits the MAPK pathway by reducing EGR1 and KLF5 levels. KLF5 is a zinc finger-containing transcription factor which is highly expressed in rapidly dividing intestinal epithelial cells. KLF5 binds to GC-rich sequences in promoters of numerous genes, such as cyclin D1, cyclin B1/Cdc2, and integrin-linked kinase. KLF5 mediates the transforming effects of oncogenic H-Ras and plays an important role in regulating colon cancer pathogenesis [1].
In vitro: In a cell-based assay for proliferation of DLD-1 cells, the IC50 of ML264 was 29 nM. In a cell-based luciferase assay, the IC50 of ML264 was 81 nM. ML264 showed no cytotoxicity in the IEC-6 control cell line with an IC50 of >50 μM. The IC50 of ML264 was 560 nM, 130 nM and 130 nM in HCT116, HT29 and SW620, respectively. ML264 significantly reduced KLF5 expression. ML264 didn’t inhibit kinases associated with the KLF5 pathway. ML264 induced death of most colon cancer cell lines, with cytotoxicity toward several other tumor cell lines as well [1].
In vivo: In an established xenograft mouse model of colon cancer, ML264 efficiently inhibited growth of the tumor within five days treatment. This effect was caused by a significant reduction in proliferation and that ML264 potently inhibited the expression of KLF5 and EGR1, a transcriptional activator of KLF5 and EGR1, a transcriptional activator of KLF5 [2].
References:
[1]. Bialkowska A, Crisp M, Madoux F, et al. ML264: An Antitumor Agent that Potently and Selectively Inhibits Krüppel-like Factor Five (KLF5) Expression: A Probe for Studying Colon Cancer Development and Progression[J]. 2013.
[2]. de Sabando A R, Wang C, He Y, et al. ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer[J]. Molecular cancer therapeutics, 2016, 15(1): 72-83.
Cell experiment: | For cell proliferation experiments, DLD-1 and HCT116 cells are treated with 10 μM ML264 or with vehicle (DMSO). Live cells are collected at 24, 48 and 72 hours post treatment and their numbers are determined by counting using a Coulter counter. Each experiment is done in triplicate. In MTS assay, DLD-1 and HCT116 cells are treated with 10 μM ML264 or with vehicle (DMSO). After 24, 48, and 72 hours of incubations, 20 μL of MTS solution is added to each well and an analysis is performed. The measurement of the control (cells with medium and DMSO) is defined as 100% and the results from other measurements are calculated accordingly. Each experiment is done in sextuplicate. A cell cycle progression assay is performed. Each experiment is done in triplicate. The apoptosis rate is determined using the Alexa Fluor 488 Annexin V/Dead Cell Apoptosis Kit with analysis by flow cytometry. Each experiment is done in triplicate[2]. |
Animal experiment: | Mice[2]Nude mice are housed under specific pathogen-free conditions in ventilated and filtered cages under positive pressure. Xenograft tumors are generated by injecting subcutaneously 5×106 DLD-1 human colorectal cells into the right flank of 6-7 week old male nude mice. Tumor volume is determined by caliper measurement and calculated by established methods. When tumors reach a volume of about 100 mm6, mice are treated intraperitoneally (i.p.) with varying doses of ML264: 10 mg/kg daily, 10 mg/kg twice per day and 25 mg/kg twice per day, with each treatment regimen lasting for a duration of 10 days. The vehicle solution is used as the control treatment. Mice are monitored and weighed every two days. Experiments are terminated when the tumor’s greatest measurement reaches 2 cm. Tumors are excised and retained for further analyses[2]. |
References: [1]. Bialkowska A, et al. ML264: An Antitumor Agent that Potently and Selectively Inhibits Krüppel-like Factor Five (KLF5) Expression: A Probe for Studying Colon Cancer Development and Progression. | |
| Cas No. | 1550008-55-3 | SDF | |
| 别名 | (2E)-3-(3-氯苯基)-N-[2-[甲基(四氢-1,1-二氧代-2H-噻喃-4-基)氨基]-2-氧代乙基]-2-丙烯酰胺 | ||
| 化学名 | (2E)-3-(3-chlorophenyl)-N-[2-[methyl(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)amino]-2-oxoethyl]-2-propenamide | ||
| Canonical SMILES | ClC1=CC=CC(/C=C/C(NCC(N(C)C2CCS(CC2)(=O)=O)=O)=O)=C1 | ||
| 分子式 | C17H21ClN2O4S | 分子量 | 384.9 |
| 溶解度 | ≤10mg/ml in DMSO;15mg/ml in dimethyl formamide | 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 | 2.5981 mL | 12.9904 mL | 25.9808 mL |
| 5 mM | 0.5196 mL | 2.5981 mL | 5.1962 mL |
| 10 mM | 0.2598 mL | 1.299 mL | 2.5981 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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet