HC Toxin
(Synonyms: 玉米圆斑病菌毒素) 目录号 : GC43806
Potent HDAC inhibitor
Cas No.:83209-65-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
HC Toxin is a cell-permeable, reversible inhibitor of histone deacetylases (HDACs) (IC50 = 30 nM). Through its effects on HDACs, HC toxin has been shown to up-regulate the expression of 15-lipoxygenase-1 in colorectal cancer cells and induce fetal hemoglobin in human primary erythroid cells. HC Toxin is a cyclic tetrapeptide first isolated from H. carbonum (now C. carbonum), a pathogen of maize.
| Cas No. | 83209-65-8 | SDF | |
| 别名 | 玉米圆斑病菌毒素 | ||
| Canonical SMILES | [H][C@@]12C(N([H])[C@@H](C)C(N([H])[C@H](C)C(N([H])[C@](CCCCCC([C@@H]3CO3)=O)([H])C(N1CCC2)=O)=O)=O)=O | ||
| 分子式 | C21H32N4O6 | 分子量 | 436.5 |
| 溶解度 | DMSO: 10 mg/ml,Methanol: 10 mg/ml | 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 | 2.291 mL | 11.4548 mL | 22.9095 mL |
| 5 mM | 0.4582 mL | 2.291 mL | 4.5819 mL |
| 10 mM | 0.2291 mL | 1.1455 mL | 2.291 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。
HC Toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes
J Mol Endocrinol 2015 Dec;55(3):197-207.PMID:26373795DOI:10.1530/JME-15-0140.
Exercise enhances numerous signalling pathways and activates substrate metabolism in skeletal muscle. Small molecule compounds that activate these cellular responses have been shown to recapitulate the metabolic benefits of exercise. In this study, a histone deacetylase (HDAC) inhibitor, HC Toxin, was investigated as a small molecule compound that activates exercise-induced adaptations. In C2C12 myotubes, HC Toxin treatment activated two exercise-stimulated pathways: AMP-activated protein kinase (AMPK) and Akt pathways. HC Toxin increased the protein content and phosphorylation of insulin receptor substrate 1 as well as the activation of downstream Akt signalling. The effects of HC Toxin on IRS1-Akt signalling were PI3K-dependent as wortmannin abolishes its effects on IRS1 protein accumulation and Akt phosphorylation. HC toxin-induced Akt activation was sufficient to enhance downstream mTOR complex 1 (mTORC1) signalling including p70S6K and S6, which were consistently abolished by PI3K inhibition. Insulin-stimulated glucose uptake, glycolysis, mitochondrial respiration and fatty acid oxidation were also enhanced in HC toxin-treated myotubes. When myotubes were challenged with serum starvation for the induction of atrophy, HC Toxin treatment prevented the induction of genes that are involved in autophagy and proteasomal proteolysis. Conversely, IRS1-Akt signalling was not induced by HC Toxin in several hepatoma cell lines, providing evidence for a favourable safety profile of this small molecule. These data highlight the potential of HDAC inhibitors as a novel class of small molecules for the induction of exercise-like signalling pathways and metabolism.
Histone deacetylase inhibitor screening identifies HC Toxin as the most effective in intrahepatic cholangiocarcinoma cells
Oncol Rep 2016 May;35(5):2535-42.PMID:26935789DOI:10.3892/or.2016.4636.
Histone deacetylases (HDACs) are highly expressed in intrahepatic cholangiocarcinoma (ICC) and are associated with poor prognosis of these patients. The aim of the present study was to explore the inhibitory effects of HDAC inhibitors on ICC cells and identify effective and sensitive drugs for ICC. Effects of 34 HDAC inhibitors were screened through two rounds of cell viability assays, and HC Toxin, a cyclic tetrapeptide first isolated from the secondary metabolite of Helminthosporium carbonum, exhibited an antitumor activity superior to that of the other HDAC inhibitors and gemcitabine. The mechanisms involved in the inhibitory effects of HC Toxin on CCLP-1 cells were investigated by cell counting, colony formation assay, cell morphological observation, real-time PCR, western blotting and flow cytometry. It was demonstrated that HC Toxin inhibited the cell proliferation and clone formation ability of the CCLP-1 cells. HC Toxin increased the acetyl-histone H4 level and this was associated with the inhibitory effect of HC Toxin on the CCLP-1 cells. We also found that HC Toxin reduced the level of HDAC1 protein in a post-transcriptional manner. Morphological observation showed multiple morphological changes and indicated the possibility of cell differentiation owing to HC Toxin. With increasing concentration of HC Toxin, the cell cycle was gradually arrested at the G0/G1 stage and the percentage of apoptotic cells increased which was not mainly through the caspase-3-dependent ways. These results indicated that HC Toxin was the most effective among the various HDAC inhibitors with multiple functions in the suppression of ICC in vitro. Thus, HC may be a potential chemotherapeutic for ICC.
Inhibition of maize histone deacetylases by HC Toxin, the host-selective toxin of Cochliobolus carbonum
Plant Cell 1995 Nov;7(11):1941-50.PMID:8535144DOI:10.1105/tpc.7.11.1941.
HC Toxin, the host-selective toxin of the maize pathogen Cochliobolus carbonum, inhibited maize histone deacetylase (HD) at 2 microM. Chlamydocin, a related cyclic tetrapeptide, also inhibited HD activity. The toxins did not affect histone acetyltransferases. After partial purification of histone deacetylases HD1-A, HD1-B, and HD2 from germinating maize embryos, we demonstrated that the different enzymes were similarly inhibited by the toxins. Inhibitory activities were reversibly eliminated by treating toxins with 2-mercaptoethanol, presumably by modifying the carbonyl group of the epoxide-containing amino acid Aeo (2-amino-9,10-epoxy-8-oxodecanoic acid). Kinetic studies revealed that inhibition of HD was of the uncompetitive type and reversible. HC Toxin, in which the epoxide group had been hydrolyzed, completely lost its inhibitory activity; when the carbonyl group of Aeo had been reduced to the corresponding alcohol, the modified toxin was less active than native toxin. In vivo treatment of embryos with HC Toxin caused the accumulation of highly acetylated histone H4 subspecies and elevated acetate incorporation into H4 in susceptible-genotype embryos but not in the resistant genotype. HDs from chicken and the myxomycete Physarum polycephalum were also inhibited, indicating that the host selectivity of HC Toxin is not determined by its inhibitory effect on HD. Consistent with these results, we propose a model in which HC Toxin promotes the establishment of pathogenic compatibility between C. carbonum and maize by interfering with reversible histone acetylation, which is implicated in the control of fundamental cellular processes, such as chromatin structure, cell cycle progression, and gene expression.
In vitro screening of 65 mycotoxins for insecticidal potential
PLoS One 2021 Mar 18;16(3):e0248772.PMID:33735295DOI:10.1371/journal.pone.0248772.
The economic losses and threats to human and animal health caused by insects and the pathogens transmitted by them require effective and environmentally-friendly methods of controlling them. One such group of natural biocontrol agents which may be used as biopesticides is that of the entomopathogenic fungi and their toxic secondary metabolites (mycotoxins). The present in vitro work examined the insecticidal potential of 65 commercially-available mycotoxins against the insect Sf-9 cell line. Mammalian Caco-2 and THP-1 cell lines served as reference controls to select insecticidal mycotoxins harmless to mammalian cells. All tested mycotoxins significantly reduced the in vitro proliferation of the Sf-9 cells and evoked morphological changes. Ten of the mycotoxins found to strongly inhibit Sf-9 proliferation also had moderate or no effect on Caco-2 cells. The THP-1 cells were highly resistant to the tested mycotoxins: doses 103 times higher were needed to affect viability and morphology (1 μg/ml for THP-1 versus 1 ng/ml for Sf-9 and Caco-2). Nine mycotoxins significantly decreased Sf-9 cell proliferation with minor effects on mammalian cells: cyclosporins B and D, cytochalasin E, gliotoxin, HC Toxin, paxilline, penitrem A, stachybotrylactam and verruculogen. These may be good candidates for future biopesticide formulations.