Ascochlorin
(Synonyms: 壳二孢氯素,Ilicicolin D) 目录号 : GC40715An isoprenoid antibiotic and antiviral
Cas No.:26166-39-2
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
Ascochlorin is an isoprenoid antibiotic and antiviral that has diverse effects on mammalian cells. It suppresses PMA-induced invasion in renal carcinoma cells (IC50 = ~10 µM) by inhibiting the expression of matrix metalloproteinase-9. At 2 µM, ascochlorin profoundly increases the expression of p53 by increasing protein stability in cancer cells, and, at 50 µm, it inhibits signaling through STAT3. Ascochlorin also binds and inhibits the mitochondrial cytochrome bc1 complex, blocking reduction of cytochrome b by ubiquinone.
| Cas No. | 26166-39-2 | SDF | |
| 别名 | 壳二孢氯素,Ilicicolin D | ||
| Canonical SMILES | OC1=C(Cl)C(C)=C(C([H])=O)C(O)=C1C/C=C(C)/C=C/[C@]2(C)[C@@H](C)C(CC[C@H]2C)=O | ||
| 分子式 | C23H29ClO4 | 分子量 | 404.9 |
| 溶解度 | DMF: Soluble,DMSO: Soluble,Ethanol: Soluble,Methanol: Soluble | 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 | 2.4697 mL | 12.3487 mL | 24.6975 mL |
| 5 mM | 0.4939 mL | 2.4697 mL | 4.9395 mL |
| 10 mM | 0.247 mL | 1.2349 mL | 2.4697 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。
Ascochlorin induces caspase-independent necroptosis in LPS-stimulated RAW 264.7 macrophages
J Ethnopharmacol 2019 Jul 15;239:111898.PMID:31028855DOI:10.1016/j.jep.2019.111898.
Ethnopharmacological relevance: Plant-specific fungus of natural compound of Ascochyta viciae has traditionally been used in the treatment of sleeping sickness and tumors. The anti-tumor activities of the compounds obtained from Pisum sativum L were evaluated in this study. Aim of the study: In this study, during the prolonged incubation, treatment of the LPS-stimulated tumor-like macrophage RAW 264.7 cells with ASC exhibited the shift of anti-inflammatory behavior to a type of necroptotic cell death named necroptosis. Materials and methods: Ascochlorin (ASC) purified from plant-specific fungus Ascochyta viciae is a natural compound with the trimethyl oxocyclohexyl structure and an anti-cancer and antibiotic agent. The fungus contributes to the Ascochyta blight disease complex of pea (Pisum sativum L). RAW 264.7 cells have been stimulated with LPS and treated with ASC. Cell viability of the LPS-treated RAW 264.7 cells and bone marrow-derived macrophage (BMDM) cells were examined. Flow cytometry analysis with 7AAD and Annexin V was examined for the apoptotic or necroptosis/late-apoptosis. Cleaved caspase-3, -7 and -8 as well as cleaved PARP were assessed with a caspase inhibitor, z-VAD-fmk. LPS-responsible human leukemic U937 and colon cancer SW480 and HT-29 cells were also examined for the cell viabilities. Results: Flow cytometry analysis after Annexin V and 7AAD double staining showed that ASC alone induces apoptosis in RAW 264.7 cells, while it induces necroptosis/late-apoptosis in LPS-treated RAW 264.7 cells. 7AAD and Annexin V positive populations were increased in the LPS-treated cells with ASC. Although viability of LPS-treated cells with ASC was decreased, the amounts of cleaved caspase-3, -7 and -8 as well as cleaved PARP were reduced when compared with ASC-treated cells. Upon ASC treatment, the cleaved caspase-8 level was not changed, however, cleaved caspase-3, -7, and PARP were reduced in LPS-stimulated RAW 264.7 cells treated with ASC, claiming a caspase-8 independent necroptosis of ASC. Furthermore, ASC and LPS-cotreated cells which a caspase inhibitor, z-VAD-fmk, was pretreated, showed the decreased cell viability compared with control cells without the inhibitor. Cell viability of RAW 264.7 cells co-treated with ASC and LPS when treated with z-VAD was decreased. In the LPS-responsible human leukemic U937 and colon cancer SW480 and HT-29 cells, cell viabilities were decreased by 10 μM ASC. Conclusion: Prolonged stimulation of ASC with LPS induces the necroptosis in RAW cells. Activated immune cells may share the susceptibility of antitumor agents with the cancer cells.
Bioactive Ascochlorin Analogues from the Marine-Derived Fungus Stilbella fimetaria
Mar Drugs 2021 Jan 20;19(2):46.PMID:33498522DOI:10.3390/md19020046.
The marine-derived fungus Stilbella fimetaria is a chemically talented fungus producing several classes of bioactive metabolites, including meroterpenoids of the Ascochlorin family. The targeted dereplication of fungal extracts by UHPLC-DAD-QTOF-MS revealed the presence of several new along with multiple known Ascochlorin analogues (19-22). Their structures and relative configuration were characterized by 1D and 2D NMR. Further targeted dereplication based on a novel 1,4-benzoquinone sesquiterpene derivative, fimetarin A (22), resulted in the identification of three additional fimetarin analogues, fimetarins B-D (23-25), with their tentative structures proposed from detailed MS/HRMS analysis. In total, four new and eight known Ascochlorin/fimetarin analogues were tested for their antimicrobial activity, identifying the analogues with a 5-chloroorcylaldehyde moiety to be more active than the benzoquinone analogue. Additionally, the presence of two conjugated double bonds at C-2'/C-3' and C-4'/C-5' were found to be essential for the observed antifungal activity, whereas the single, untailored bonds at C-4'/C-5' and C-8'/C-9' were suggested to be necessary for the observed antibacterial activity.
Molecular Targets of Ascochlorin and Its Derivatives for Cancer Therapy
Adv Protein Chem Struct Biol 2017;108:199-225.PMID:28427561DOI:10.1016/bs.apcsb.2017.01.001.
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta viciae, and its synthetic derivatives have recently demonstrated substantial antineoplastic effects in a variety of tumor cell lines and mouse models. The major focus of this review article is to briefly analyze the chemopreventive as well as therapeutic properties of ASC and its derivatives and to identify the multiple molecular targets modulated by this novel class of anticancer agent.
Ascochlorin activates p53 in a manner distinct from DNA damaging agents
Int J Cancer 2009 Jun 15;124(12):2797-803.PMID:19253369DOI:10.1002/ijc.24259.
Ascochlorin, a prenylphenol antitumor antibiotic, profoundly increases the expression of endogenous p53 by increasing protein stability in the human osteosarcoma cells and human colon cancer cells. Ascochlorin also increases DNA binding activity to the p53 consensus sequence in nuclear extract and enhances transcription of p53 downstream targets. Ascochlorin specifically induces p53 phosphorylation at ser 392 without affecting ser 15 or 20, whereas DNA damaging agents typically phosphorylate these serines. Moreover, Ascochlorin does not induce phosphorylation of ATM and CHK1, an established substrate of ATR that is activated by genotoxins, nor does it increase DNA strand break, as confirmed by comet assay. The structure-activity relationship suggests that p53 activation by Ascochlorin is related to inhibition of mitochondrial respiration, which is further supported by the observation that respiratory inhibitors activate p53 in a manner similar to Ascochlorin. These results suggest that Ascochlorin, through the inhibition of mitochondrial respiration, activates p53 through a mechanism distinct from genotoxins.
Ascochlorin, an isoprenoid antibiotic, induces G1 arrest via downregulation of c-Myc in a p53-independent manner
Biochem Biophys Res Commun 2010 Jul 16;398(1):68-73.PMID:20558137DOI:10.1016/j.bbrc.2010.06.037.
Numerous anti-cancer agents inhibit cell cycle progression via a p53-dependent mechanism; however, many of these carcinostatic substances are toxic. Here, we show that Ascochlorin, an isoprenoid antibiotic, is a non-toxic anti-cancer agent that induces G1 arrest via the induction of p21(WAF1/CIP1) in a c-Myc, but not a p53, dependent manner. Ascochlorin has a broad spectrum of anti-tumor and anti-metastatic activities, but the molecular mechanism by which it inhibits cell cycle progression of cancer cells remains to be elucidated. We demonstrated that cytostatic G1 arrest by Ascochlorin is mainly associated with the upregulation of p21(WAF1/CIP1), and the downregulation of c-Myc. Furthermore, we used a chromatin immunoprecipitation assay, RNA interference, and p53-deficient cells to verify that p21(WAF1/CIP1) induction by Ascochlorin is related to transcriptional repression of c-Myc. Ascochlorin abolished pRB hyperphosphorylation, which resulted in the inactivation of E2F transcriptional activity. These results suggest that Ascochlorin induces G1 arrest via the p53-independent suppression of c-Myc. Thus, we reveal a role for Ascochlorin in inhibiting tumor growth via G1 arrest, and identify a novel regulatory mechanism for c-Myc.