Enviroxime
(Synonyms: LY122772) 目录号 : GC47295An antiviral agent
Cas No.:72301-79-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Enviroxime is an antiviral agent.[1] It inhibits coxsackievirus B3-, rhinovirus-, or poliovirus-induced plaque formation in HeLa monolayer cell cultures when used at concentrations of 0.1, 1, and 10 µg/ml.1 Enviroxime (1 µg/ml) inhibits production of poliovirus PV1 viral RNA in HeLa monolayer cell cultures. It reduces viral titers in DRAW macrophages infected with the DA strain of Theiler’s murine encephalomyelitis virus.[2]
Reference:
[1].Heinz, B.A., and Vance, L.M.The antiviral compound enviroxime targets the 3A coding region of rhinovirus and poliovirusJ. Virol.69(7)4189-4197(1995) 2.Steurbaut, S., Merckx, E., Rombaut, B., et al.Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler’s murine encephalomyelitis virusVirol. J.589(2008)
| Cas No. | 72301-79-2 | SDF | |
| 别名 | LY122772 | ||
| 化学名 | (1E)-[2-amino-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-6-yl]phenyl-methanone oxime | ||
| Canonical SMILES | O/N=C(C1=CC=C(N=C(N)N2S(C(C)C)(=O)=O)C2=C1)\C3=CC=CC=C3 | ||
| 分子式 | C17H18N4O3S | 分子量 | 358.4 |
| 溶解度 | DMSO: soluble, Methanol: slightly, heated | 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 | 2.7902 mL | 13.9509 mL | 27.9018 mL |
| 5 mM | 0.558 mL | 2.7902 mL | 5.5804 mL |
| 10 mM | 0.279 mL | 1.3951 mL | 2.7902 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。
Topical Enviroxime against rhinovirus infection
Antimicrob Agents Chemother 1982 Dec;22(6):1004-7.PMID:6297380DOI:10.1128/AAC.22.6.1004.
Enviroxime, an inhibitor of rhinovirus replication, was studied in a double-blind, placebo-controlled trial with 99 volunteers. The efficacy of a nasal-spray formulation of Enviroxime was tested as pretreatment or as postchallenge treatment for rhinovirus type 4 infection. In the regimens used, drug administration neither prevented infection nor reduced the frequency of specific colds. The mean concentration of Enviroxime in nasal washes (12 h after a dose) differentiated two groups of responders. Those in whom the drug concentration exceeded 100 ng/ml had some benefits, although these were statistically insignificant.
PI4KIII inhibitor Enviroxime impedes the replication of the hepatitis C virus by inhibiting PI3 kinases
J Antimicrob Chemother 2018 Dec 1;73(12):3375-3384.PMID:30219827DOI:10.1093/jac/dky327.
Objectives: Many positive-stranded RNA viruses, including HCV, drastically remodel intracellular membranes to generate specialized environments for RNA replication. Phosphatidylinositol 4-kinase III (PI4KIII)α plays an essential role in the formation of HCV replication complexes and has therefore been explored as a potential drug target. Here, we characterized the anti-HCV activity of the PI4KIII inhibitors Enviroxime and BF738735 and elucidated their mechanism of action. Methods: Antiviral assays were performed using HCV subgenomic replicons and infectious HCV. Enviroxime- and BF738735-resistant HCV replicons were generated by long-term culture with increasing compound concentrations. Intracellular localization of phosphatidylinositol 4-phosphate (PI4P) lipids was analysed by confocal microscopy. Results: HCV subgenomic replicons resistant to either Enviroxime or BF738735 proved cross-resistant and carried mutations in the NS3, NS4B and NS5A genes. Knockdown of PI4KIIIβ by small interfering RNA (siRNA) did not affect the replication of the HCV subgenomic replicon in this study. Furthermore, the compounds did not affect PI4P lipid levels at the replication complexes nor the phosphorylation status of NS5A, activities attributed to PI4KIIIα. Interestingly, the broad-spectrum phosphoinositide 3-kinase (PI3K) inhibitor LY294002 proved to be 10-fold less effective against the resistant replicons. In addition, Enviroxime and BF738735 inhibited several PI3Ks in enzymatic assays. Conclusions: Contrary to assumptions, our data indicate that PI4KIIIα and PI4KIIIβ are not the main targets for the anti-HCV activity of Enviroxime and BF738735. Instead, we demonstrated that both molecules impede HCV replication at least partially by an inhibitory effect on PI3Ks. Moreover, HCV is able to bypass PI3K inhibition by acquiring mutations in its genome.
Oxysterol-binding protein family I is the target of minor enviroxime-like compounds
J Virol 2013 Apr;87(8):4252-60.PMID:23365445DOI:10.1128/JVI.03546-12.
Enviroxime is an antipicornavirus compound that targets host phosphatidylinositol 4-kinase III beta (PI4KB) activity for its antipicornavirus activity. To date, several antipoliovirus (PV) compounds similar to Enviroxime that are associated with a common resistance mutation in viral protein 3A (a G5318A [3A-Ala70Thr] mutation in PV) have been identified. Most of these compounds have a direct inhibitory effect on PI4KB activity, as well as Enviroxime (designated major enviroxime-like compounds). However, one of the compounds, AN-12-H5, showed no inhibitory effect on PI4KB and was considered to belong to another group of enviroxime-like compounds (designated minor enviroxime-like compounds). In the present study, we performed a small interfering RNA (siRNA) sensitization assay targeting PI4KB-related genes and identified oxysterol-binding protein (OSBP) as a target of minor enviroxime-like compounds. Knockdown of OSBP and OSBP2 increased the anti-PV activities of AN-12-H5 and a newly identified minor enviroxime-like compound, T-00127-HEV2, and also to T-00127-HEV1 to a minor extent, in the cells. A ligand of OSBP, 25-hydroxycholesterol (25-HC), acted as a minor enviroxime-like compound. Minor enviroxime-like compounds induced relocalization of OSBP to the Golgi apparatus in cells. Treatment of the cells with major or minor enviroxime-like compounds suppressed the expression of genes (HMGCS1 and SQLE) in the SREBP/SCAP regulatory pathway and diminished endogenous phosphatidylinositol 4-phosphate (PI4P) at the Golgi apparatus. Our results suggested that minor enviroxime-like compounds are phenotypically identical to 25-HC and that major and minor enviroxime-like compounds suppress the production and/or accumulation of PI4P in PV-infected cells by targeting PI4KB and OSBP family I activities, respectively.
Evidence that Enviroxime targets multiple components of the rhinovirus 14 replication complex
Arch Virol 1999;144(8):1569-85.PMID:10486111DOI:10.1007/s007050050611.
Enviroxime and related analogs are potent inhibitors of rhinoviruses and enteroviruses in cell culture. Previous analyses of resistant mutants implicated the viral nonstructural protein 3A(B) as the likely target of drug activity. In this study, we used site-directed mutagenesis and selection of spontaneous rhinovirus 14 mutants with several Enviroxime analogs to confirm the link between domains in rhinovirus 14 3A(B) and the function blocked by Enviroxime. We also produced recombinant 3A and 3AB proteins for biochemical analyses. Despite extensive efforts, however, we were unable to demonstrate direct binding between Enviroxime and any of several viral proteins, nor could we demonstrate binding of Enviroxime to a host protein. In addition, Enviroxime did not disrupt 3AB's ability to bind RNA or 3D polypeptide, the association of 3AB with membranes, or the cleavage of 3AB by 3C protease. Finally, we identified an enviroxime-resistant mutant with an increased level of resistance which apparently has mutations in multiple proteins or RNA sequences. Taken together, these results suggest that Enviroxime targets a complex of proteins and/or cellular factors. Such a complex mechanism of inhibition might explain the low levels of viral resistance to these inhibitors as compared with other picornaviral inhibitors.
Therapeutic activity of Enviroxime against rhinovirus infection in volunteers
Antimicrob Agents Chemother 1983 May;23(5):671-5.PMID:6870216DOI:10.1128/AAC.23.5.671.
The therapeutic effect of intranasal 2-amino-1-(isopropylsulphonyl)-6-benzimidazole phenyl ketone oxime (Enviroxime) against human rhinovirus type 9 was evaluated in a double-blind, placebo-controlled volunteer trial. Enviroxime given 6 times a day was well tolerated, producing a reduction in clinical evidence of infection which coincided with the start of medication (44 h after virus challenge). Although there was a statistically significant reduction in clinical score in the Enviroxime group on day 5 after virus challenge, reductions in total clinical score accumulated during the trial and reductions in the quantity of nasal secretions were not significant. A separate analysis was performed on data from volunteers who did not have symptoms when medication began (and who might have been expected to benefit more from Enviroxime therapy). No apparent enhancement of the effects of Enviroxime could be demonstrated in this group.