EN4
目录号 : GC62287
EN4, a covalent ligand that targets cysteine 171 (C171) of MYC, is selective for c-MYC over N-MYC and L-MYC. EN4 inhibits MYC transcriptional activity, downregulates MYC targets, and impairs tumorigenesis.
Cas No.:1197824-15-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >96.00%
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EN4, a covalent ligand that targets cysteine 171 (C171) of MYC, is selective for c-MYC over N-MYC and L-MYC. EN4 inhibits MYC transcriptional activity, downregulates MYC targets, and impairs tumorigenesis.
EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. EN4 treatment significantly impairs 231MFP breast cancer cell proliferation in a dose- and time-dependent manner. EN4 impairs the cell survival of MYC transformed mammary epithelial MCF10A cells, but not parental MCF10A cells that are not dependent on MYC.[1]
EN4 treatment initiated after establishment of a 231MFP breast tumor xenograft in immune-deficient mice also significantly attenuates tumor growth in vivo.[1]
[1] Lydia Boike, et al. Cell Chem Biol. 2021 Jan 21;28(1):4-13.e17.
| Cas No. | 1197824-15-9 | SDF | |
| 分子式 | C25H24N2O4 | 分子量 | 416.47 |
| 溶解度 | DMSO : 250 mg/mL (600.28 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light |
| 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 | 2.4011 mL | 12.0057 mL | 24.0113 mL |
| 5 mM | 0.4802 mL | 2.4011 mL | 4.8023 mL |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4011 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。
Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC
Cell Chem Biol 2021 Jan 21;28(1):4-13.e17.PMID:32966806DOI:10.1016/j.chembiol.2020.09.001.
MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. Here, we have performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt the binding of MYC to its DNA consensus sequence in vitro and also impair MYC transcriptional activity in situ in cells. We have identified a covalent ligand, EN4, that targets cysteine 171 of MYC within a predicted intrinsically disordered region of the protein. We show that EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. We also show initial structure-activity relationships of EN4 and identify compounds that show improved potency. Overall, we identify a unique ligandable site within an intrinsically disordered region of MYC that leads to inhibition of MYC transcriptional activity.
Effect of lysin EN4 in combination with sodium bicarbonate on reduction of Salmonella in chilled and thawed chicken meat
Int J Food Microbiol 2023 Feb 16;387:110058.PMID:36543012DOI:10.1016/j.ijfoodmicro.2022.110058.
Lysin EN4 is a peptidoglycan-degrading enzyme. Like other lysins against Gram-negative bacteria, EN4 requires cell-wall destabilizing agents, such as ethylenediamine tetraacetic acid (EDTA) to facilitate it to the peptidoglycan layer. This study aimed to use EN4 in reducing Salmonella in chilled and thawed raw chicken meat. However, the use of EDTA is limited to some types of foods. An alternative to EDTA was explored. Sodium bicarbonate was identified as an effective alternative to EDTA. The combination of EN4 with 0.1 % NaHCO3, pH 7.4 showed a wide lytic spectrum against Salmonella spp. The combination showed efficiency in reduction of Salmonella Enteritidis and Typhimurium in raw chicken meat during storage at 4 °C for 48 h, with the maximum reduction of 1.0-1.3log CFU/g. The efficiency of the combination against Salmonella was evaluated in frozen chicken meat during proper and improper defrosting. A significant reduction of Salmonella was observed in EN4-treated meat compared to the untreated control through 48 and 4 h of defrosting at 4 and 30 °C, respectively, with the greatest reduction of 1.2-1.6 log CFU/g. The results indicated that EN4 in combination with NaHCO3 has a potential use for controlling growth of Salmonella in chilled and thawed chicken meat.
Characterization of EN4 monoclonal antibody: a reagent with CD31 specificity
Clin Exp Immunol 1994 Apr;96(1):170-6.PMID:7512006DOI:10.1111/j.1365-2249.1994.tb06248.x.
EN4 MoAb was originally described as a MoAb that reacts specifically with human endothelial cells, and the reagent was not assigned to any of the presently known CD. Here, we provide evidence indicating that EN4 reacts with the CD31 antigen. Thus, EN4 stains strongly murine fibroblasts transfected with the human CD31 gene. Furthermore, SDS-PAGE analysis of immunoprecipitates of cell lysates from surface-iodinated Jurkart T cells demonstrated that EN4 and reference CD31 MoAb recognized the same antigen, of 130 kD mol. wt. Finally, both EN4 and CD31 gave the same pattern of reactivity when tested on tonsillar or peripheral blood lymphoid cells by FACS analysis or by immunohistochemistry on sections of a variety of human tissues. EN4, however, proved consistently more efficient than the reference anti-CD31 MoAb as judged by both the intensity of fluorescence or of tissue staining. This property has thus allowed a better characterization of the tissue and cellular distribution of CD31.
Antimicrobial properties of 8-hydroxyserrulat-14-en-19-oic acid for treatment of implant-associated infections
Antimicrob Agents Chemother 2013 Jan;57(1):333-42.PMID:23114780DOI:10.1128/AAC.01735-12.
Treatment options are limited for implant-associated infections (IAI) that are mainly caused by biofilm-forming staphylococci. We report here on the activity of the serrulatane compound 8-hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene isolated from the Australian plant Eremophila neglecta. EN4 elicited antimicrobial activity toward various Gram-positive bacteria but not to Gram-negative bacteria. It showed a similar bactericidal effect against logarithmic-phase, stationary-phase, and adherent Staphylococcus epidermidis, as well as against methicillin-susceptible and methicillin-resistant S. aureus with MICs of 25 to 50 μg/ml and MBCs of 50 to 100 μg/ml. The bactericidal activity of EN4 was similar against S. epidermidis and its Δica mutant, which is unable to produce polysaccharide intercellular adhesin-mediated biofilm. In time-kill studies, EN4 exhibited a rapid and concentration-dependent killing of staphylococci, reducing bacterial counts by >3 log(10) CFU/ml within 5 min at concentrations of >50 μg/ml. Investigation of the mode of action of EN4 revealed membranolytic properties and a general inhibition of macromolecular biosynthesis, suggesting a multitarget activity. In vitro-tested cytotoxicity on eukaryotic cells was time and concentration dependent in the range of the MBCs. EN4 was then tested in a mouse tissue cage model, where it showed neither bactericidal nor cytotoxic effects, indicating an inhibition of its activity. Inhibition assays revealed that this was caused by interactions with albumin. Overall, these findings suggest that, upon structural changes, EN4 might be a promising pharmacophore for the development of new antimicrobials to treat IAI.
HMEC-1: establishment of an immortalized human microvascular endothelial cell line
J Invest Dermatol 1992 Dec;99(6):683-90.PMID:1361507DOI:10.1111/1523-1747.ep12613748.
The study of human microvascular endothelial cells has been limited, because these cells are difficult to isolate in pure culture, are fastidious in their in vitro growth requirements, and have a very limited lifespan. In order to overcome these difficulties, we have transfected human dermal microvascular endothelial cells (HMEC) with a PBR-322-based plasmid containing the coding region for the simian virus 40 A gene product, large T antigen, and succeeded in immortalizing them. These cells, termed CDC/EU.HMEC-1 (HMEC-1), have been passaged 95 times to date and show no signs of senescence, whereas normal microvascular endothelial cells undergo senescence at passages 8-10. HMEC-1 exhibit typical cobblestone morphology when grown in monolayer culture, express and secrete von Willebrand's Factor, take up acteylated low-density lipoprotein, and rapidly form tubes when cultured on matrigel. HMEC-1 grow to densities three to seven times higher than microvascular endothelial cells and require much less stringent growth medium. HMEC-1 will grow in the absence of human serum, whereas microvascular endothelial cells require culture medium supplemented with 30% human serum. These cells express other cell-surface molecules typically associated with endothelial cells, including CD31 and CD36 and epitopes identified by monoclonal antibodies EN4 and PAL-E. They also express the cell adhesion molecules ICAM-1 and CD44 and following stimulation with interferon-gamma express major histocompatibility complex class II antigens. HMEC-1 specifically bind lymphocytes in cell adhesion assays. Thus HMEC-1 is the first immortalized human microvascular endothelial cell line that retains the morphologic, phenotypic, and functional characteristics of normal human microvascular endothelial cells.