Heptelidic Acid
(Synonyms: 萜烯七脂酸; Koningic acid) 目录号 : GC43816A selective, irreversible GAPDH inhibitor
Cas No.:57710-57-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in carbohydrate metabolism, reversibly catalyzes the conversion of GAP to 1,3-bisphosphoglycerate and NAD+. Heptelidic acid is a sesquiterpene lactone produced by the fungus T. koningii that was shown to have antibiotic activity against anaerobic bacteria such as Bacteroides. It acts as an irreversible inhibitor of GAPDH that binds to the cysteine-149 residue at the active site of the enzyme (Ki = 1.6 µM). It can selectively induce apoptosis in high-glycolytic cancer cells by inhibiting the generation of ATP in the glycolytic pathway. Heptelidic acid is also a selective and competitive inhibitor of mammalian DNA polymerases β and λ as well as terminal deoxynucleotidyl transferase in family X of DNA polymerases (Kis range from 5.2-9.5 µM).
| Cas No. | 57710-57-3 | SDF | |
| 别名 | 萜烯七脂酸; Koningic acid | ||
| Canonical SMILES | CC(C)[C@H]1CC[C@@]2(CO2)[C@]3([H])[C@]1([H])C=C(C(O)=O)COC3=O | ||
| 分子式 | C15H20O5 | 分子量 | 280.3 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 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 | 3.5676 mL | 17.838 mL | 35.6761 mL |
| 5 mM | 0.7135 mL | 3.5676 mL | 7.1352 mL |
| 10 mM | 0.3568 mL | 1.7838 mL | 3.5676 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。
Evaluation of Heptelidic Acid as a potential inhibitor for tau aggregation-induced Alzheimer's disease and associated neurotoxicity
Int J Biol Macromol 2021 Jul 31;183:1155-1161.PMID:33971235DOI:10.1016/j.ijbiomac.2021.05.018.
Tau is a major component of protein plaques in tauopathies, especially Alzheimer's disease (AD). The purpose of the present study is to explore the inhibitory effects of Heptelidic Acid as a bioactive compound from fungus T. koningii on tau fibrillization and associated neurotoxicity. The influences of various concentrations of Heptelidic Acid on tau fibrillization and underlying neurotoxicity were explored by assessment of the biophysical (ThT/Nile red fluorescence, CR absorbance, CD, and TEM) and cellular (MTT, LDH, and caspase-3) assays. It was shown that Heptelidic Acid inhibited tau fibrillization in a concentration-dependent manner. On the other hand, cellular assays indicated that the viability, LDH release, and caspase-3 activity were regulated when neurons were exposed to tau samples co-incubated with Heptelidic Acid. In conclusion, it may be indicated that Heptelidic Acid inhibited tau fibrillization which was accompanied by formation of amorphous aggregated species of tau with much less neurotoxicity than tau amyloid alone. Thus, Heptelidic Acid can be considered as a potential candidate in preventive care studies to inhibit the formation of tau plaques as neurotoxic species.
Furan, phenolic, and Heptelidic Acid derivatives produced by Aspergillus oryzae
Food Sci Biotechnol 2016 Oct 31;25(5):1259-1264.PMID:30263403DOI:10.1007/s10068-016-0199-z.
Eleven compounds, including a new sesquiterpene, were isolated from the culture medium of Aspergillus oryzae incubated with capsaicin. The structure of the new compound was determined to be 1,3,5a,6,7,8,9,9a-octahydro-9-hydroxy-9-(hydroxymethyl)-6-isopropyl-1-oxobenzo[c]oxepine-4- carboxylic acid, a Heptelidic Acid derivative. In addition, 10 known compounds were identified, namely 5-(hydroxymethyl)-3-furancarboxylic acid (flufuran), 3-hydroxypropanoic acid, 5-(hydroxymethyl)-2- furancarboxylic acid, 2-(4-hydroxyphenyl)-ethanol, 4-hydroxybenzoic acid, vanillic acid, 3,4-dihydroxybenzoic acid, 2-furanol, hydroheptelidic acid, and trichoderonic acid A, using spectroscopic data from nuclear magnetic resonance and electrospray ionization-mass spectroscopy.
4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects
Nat Commun 2019 Nov 8;10(1):5091.PMID:31704924DOI:10.1038/s41467-019-13078-5.
Activated macrophages switch from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect, presenting a potential therapeutic target in inflammatory disease. The endogenous metabolite itaconate has been reported to regulate macrophage function, but its precise mechanism is not clear. Here, we show that 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) directly alkylates cysteine residue 22 on the glycolytic enzyme GAPDH and decreases its enzyme activity. Glycolytic flux analysis by U13C glucose tracing provides evidence that 4-OI blocks glycolytic flux at GAPDH. 4-OI thereby downregulates aerobic glycolysis in activated macrophages, which is required for its anti-inflammatory effects. The anti-inflammatory effects of 4-OI are replicated by Heptelidic Acid, 2-DG and reversed by increasing wild-type (but not C22A mutant) GAPDH expression. 4-OI protects against lipopolysaccharide-induced lethality in vivo and inhibits cytokine release. These findings show that 4-OI has anti-inflammatory effects by targeting GAPDH to decrease aerobic glycolysis in macrophages.
Probiotic-derived Heptelidic Acid exerts antitumor effects on extraintestinal melanoma through glyceraldehyde-3-phosphate dehydrogenase activity control
BMC Microbiol 2022 Apr 22;22(1):110.PMID:35459092DOI:10.1186/s12866-022-02530-0.
Background: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that Heptelidic Acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. Results: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. Conclusion: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators.
Three New Heptelidic Acid Derivatives from the Culture of Mushroom Lentinellus ursinus
Nat Prod Bioprospect 2018 Oct;8(5):355-360.PMID:29790088DOI:10.1007/s13659-018-0168-8.
Three new Heptelidic Acid derivatives (1-3) including two new dimeric esters and two known Heptelidic Acid analogues (4 and 5) were isolated from the solid culture of mushroom Lentinellus ursinus. The structures of new compounds were confirmed by the analysis of NMR and HRESIMS spectroscopic data. The biosynthetic origin of compounds 1-5 was postulated. Compounds 1-5 exhibited no antibacterial activity against Staphylococcus aureus and Escherichia coli at the dose of 100 μM.