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| 1mg |
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| Other Sizes |
| Targets |
Verrucarin J targets both cancer cells and cancer stem cells. Its mechanism involves the generation of reactive oxygen species (ROS), which induces apoptosis in cancer cell lines. The compound suppresses the expression of cancer stem cell markers, leading to a decrease in the population of these cells. As a trichothecene, it inhibits protein synthesis by binding to the 60S ribosomal subunit, which contributes to its potent cytotoxic effects.
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| ln Vitro |
In A549 cells, verrucarin J (0, 5, 10, 20, 50 nM; 24 hours) causes apoptosis [1]. The cell growth of A549 and H1793 cells was considerably decreased by verrucarin J (0, 1, 2, 5, 10, 20, 50 nM; 24, 48, 72 hours), with IC50 values of roughly 10 nM and 20 nM after 48 hours of treatment, respectively[1]. For HCT 116 and SW-620 cell growth, verrucarin J (0, 0.1, 0.2, 0.3, 0.4, 0.5 μM; 24 hours) had an IC50 of 300 nM [2]. Verrucarin J (0, 10, 20 nM, 48 hours) suppresses the expression of important CSC-specific genes (ALDH1, LGR5, OCT4, and CD133) in A549 cells and inhibits the Wnt1/β-catenin and Notch1 cancer stem cell (CSC) self-renewal pathway [1]. Compound 2, Verrucarin J, exhibits noteworthy efficacy against Candida albicans and Mucor michelia at 50 μg/disk [3]. Verrucarin J has a comparable impact against the arenavirus Tacaribe and decreases JUNV production by more than 2 log units [4]. Verrucarin J has a cytotoxic concentration 50% (CC50) of 8.2 ng/mL, which has the potential to decrease Vero cell viability [4].
Verrucarin J demonstrates potent in vitro anticancer activity. It significantly inhibits cell proliferation and induces apoptosis in cancer cell lines such as A549, HCT 116, and SW-620 cells. The compound generates reactive oxygen species (ROS), which triggers apoptotic cell death. It also suppresses the expression of cancer stem cell markers, leading to a decrease in the population of these cells. The compound shows activities against Candida albicans and Mucor miehei. Specific IC50 values and detailed assay conditions are not extensively provided. |
| ln Vivo |
In xenograft animals, intraperitoneal injection of Verrucarin J (0.5 mg/kg) for 4 weeks suppresses the growth of tumors generated by AKT [2]. Verrucarin J is an extremely potent anticancer medication that can stop tumor development and metastasis (0.1, 0.5, 2.0 mg/kg; intraperitoneally administered for three weeks) [5].
Verrucarin J demonstrates potent in vivo anticancer activity. In an ovarian cancer model, the compound significantly reduced visible peritoneal tumors by 61% compared to the control group at 0.5 mg/kg. It also highly reduced visible metastasis at 0.5 mg/kg and reduced ovarian tumor weight by 71% compared to vehicle. Verrucarin J can stop tumor development and metastasis when administered intraperitoneally at 0.1, 0.5, or 2.0 mg/kg for three weeks. However, at a lethal dose of 2 mg/kg, mice became sick with a swollen belly and subsequently died within 3 treatments. |
| Enzyme Assay |
In vitro enzyme assays for Verrucarin J are not standardly performed as the compound is a mycotoxin that acts through multiple mechanisms. As a trichothecene, it inhibits protein synthesis by binding to the 60S ribosomal subunit. This can be assessed by measuring [³H]leucine or [³⁵S]methionine incorporation into newly synthesized proteins in cell-free translation systems or in cultured cells. The compound's ability to generate ROS can be measured using fluorescent probes such as DCFH-DA. Apoptosis induction can be assessed by measuring caspase activity or by Annexin V staining. Specific protocols are not extensively documented in the available literature.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines such as A549 (lung), HCT 116 (colon), and SW-620 (colon) are cultured in appropriate medium. Cells are treated with Verrucarin J at various concentrations (typically 0.01-1000 nM) for 24-72 hours. Cell proliferation is assessed using MTT, CCK-8, or similar assays. Apoptosis is measured by Annexin V/PI staining, caspase 3/7 activity assays, or by assessing PARP cleavage by Western blot. ROS generation is measured using DCFH-DA fluorescent probe. Cancer stem cell markers (e.g., CD44, CD133, ALDH) are assessed by flow cytometry or Western blot. Cell cycle analysis is performed by propidium iodide staining and flow cytometry.
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| Animal Protocol |
Animal/Disease Models: 6-8 week old BALB/c athymic nude mice (nu/nu)[2] with pCMV/HCT 116 and AKT/HCT 116 xenografts [2]
Doses: 0.5 mg/kg body weight Route of Administration: intraperitonealResults 4 weeks after injection: diminished expression of pro-survival markers pAKT, Notch1, p65 and Ki67 in all tumors. Animal/Disease Models: Female naked nu/nu (5 to 6 weeks old) mice with A2780 xenografts [5] Doses: 0.1, 0.5, 2.0 mg/kg (Vehicle: 10% DMSO, 90% Tricaprylin Ester) Route of Administration: intraperitoneal (ip) injection three weeks. Results 10 days after injection of A2780 cells: tumor weight reduction (32% compared to control) and reduction in visible metastases at a dose of 0.1 mg/kg. At the dose of 0.5 mg/kg, a significant reduction in peritoneal tumors was seen (61% reduction compared to the control group), and a significant reduction in metastasis was seen. Ovarian tumor weight at 0.5 mg/kg was diminished by 71% compared to vehicle. At a lethal dose of 2 mg/kg, mice developed abdominal swelling, fluid swelling, and subseque In vivo animal studies for Verrucarin J use tumor xenograft models, particularly ovarian cancer models. Mice are implanted with tumor cells, and after tumors are established, Verrucarin J is administered intraperitoneally at doses of 0.1, 0.5, or 2.0 mg/kg for three weeks. Tumor volume is measured using calipers. Visible peritoneal tumors and metastases are assessed at necropsy. Tumor weight is measured. Body weight and survival are monitored. Histological examination of tumors and tissues is performed. At 0.5 mg/kg, visible peritoneal tumors are reduced by 61% and ovarian tumor weight by 71%. At 2 mg/kg, lethal toxicity is observed. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Trichothecene toxins are lipophilic, thus readily absorbed through the skin, intestines, and lung mucosa. They are primarily metabolized in the liver by cytochrome P-450 and trichothecene-specific carboxylesterases, although some metabolic activity is also observed in other tissues such as the kidneys, spleen, and intestines. Trichothecene toxins are metabolized into less toxic metabolites through reactions such as hydrolysis, hydroxylation, deepoxidation, and glucuronidation. These metabolites are excreted in urine and feces. (L1910, L1949) Verrucarin J is a trichothecene mycotoxin with molecular formula C27H32O8 and molecular weight 484.54. The compound is a white powder. Routes of exposure include oral, dermal, inhalation, and parenteral routes. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life) are not extensively characterized in the available literature. As a mycotoxin, it would be expected to be distributed widely in tissues. The compound's potent in vivo activity at low doses (0.1-0.5 mg/kg) suggests good bioavailability and tissue penetration. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Unlike many other fungal toxins, trichothecene toxins exert their biological activity without metabolic activation, instead reacting directly with cellular components. Trichothecene toxins are cytotoxic to most eukaryotic cells because they potently inhibit protein synthesis. They achieve this by freely crossing the plasma membrane and binding with a high affinity to ribosomes. Specifically, they interfere with the peptidyl transferase active site located at the 3' end of the 28S ribosomal RNA, inhibiting the initiation, elongation, or termination steps of protein synthesis and leading to polyribosome depolymerization. Protein synthesis is a fundamental function of all tissues, but tissues with active, rapidly growing, and dividing cells are particularly sensitive to these toxins. Furthermore, binding to ribosomes is thought to activate proteins in downstream signaling pathways associated with immune responses and apoptosis, such as mitogen-activated protein kinase. This is known as ribosomal toxicity stress. Trichothecene toxins may also induce changes in membrane structure, leading to increased lipid peroxidation and inhibition of mitochondrial electron transport activity. They can further induce apoptosis by generating reactive oxygen species. Other secondary effects of trichothecene toxins include inhibition of RNA and DNA synthesis and inhibition of mitosis. (L1948, L1949, A2962, A2963, A2964, A2980) Verrucarin J is an extremely potent mycotoxin with significant toxicity. At a lethal dose of 2 mg/kg, mice become sick with a swollen belly and subsequently die within 3 treatments. The compound is a trichothecene mycotoxin produced by various Fusarium species. Trichothecenes are known to be highly toxic to both animals and humans, causing gastrointestinal, dermatological, and immunological effects. Routes of exposure include oral, dermal, inhalation, and parenteral routes. The compound's potent anticancer activity is associated with significant toxicity, which may limit its therapeutic window. |
| References |
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| Additional Infomation |
Trichosporin J is a trichothecene toxin. Trichothecenes are a class of chemically related fungal toxins produced by various fungi in the genera Fusarium, Myrothecium, Trichoderma, Cephalosporium, Verticimonosporium, and Stachybotrys. The most important structural features for the biological activity of trichothecenes include: a 12,13-epoxy ring, a hydroxyl or acetyl group at an appropriate position on the trichothecene core, and the structure and position of the side chains. They are produced by various Fusarium fungi, such as F. graminearum, F. sporotrichioides, F. poae, and F. equiseti, which are found on various grains such as wheat, oats, and corn. Some molds that produce trichothecene toxins, such as Stachybotrys chartarum, can grow in humid indoor environments and may cause health problems for building occupants. (L1948)
See also: Verrucarin J (note moved to). Verrucarin J is a trichothecene mycotoxin produced by various species of Fusarium, Verticimonosporium, and Stachybotrys. It is an extremely potent anticancer agent that targets both cancer cells and cancer stem cells. The compound generates reactive oxygen species (ROS) and induces apoptosis in cancer cell lines such as A549, HCT 116, and SW-620 cells. In an ovarian cancer model, Verrucarin J at 0.5 mg/kg reduces visible peritoneal tumors by 61% and ovarian tumor weight by 71%. However, at 2 mg/kg, it is lethal. The compound also shows antimicrobial activity against Candida albicans and Mucor miehei. No approved therapeutic status is reported due to its high toxicity. |
| Molecular Formula |
C27H32O8
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| Molecular Weight |
484.53818
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| Exact Mass |
484.21
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| CAS # |
4643-58-7
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| PubChem CID |
6437363
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| Appearance |
White to off-white solid powder
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| Density |
1.297g/cm3
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| Boiling Point |
735.353°C at 760 mmHg
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| Flash Point |
312.2°C
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| LogP |
3.119
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
35
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC1=C[C@@H]2[C@@]3(CC1)COC(=O)/C=C(/CCOC(=O)/C=C/C=C/C(=O)O[C@H]4[C@]3([C@]5(CO5)[C@@H](C4)O2)C)\C
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| InChi Key |
GXCGYHWSYNQVHU-UGAPSZEOSA-N
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| InChi Code |
InChI=1S/C27H32O8/c1-17-8-10-26-15-32-24(30)13-18(2)9-11-31-22(28)6-4-5-7-23(29)35-19-14-21(34-20(26)12-17)27(16-33-27)25(19,26)3/h4-7,12-13,19-21H,8-11,14-16H2,1-3H3/b6-4+,7-5+,18-13+/t19-,20-,21-,25-,26-,27+/m1/s1
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| Chemical Name |
(1R,3R,8R,12E,18E,20E,24R,25S,26S)-5,13,25-trimethylspiro[2,10,16,23-tetraoxatetracyclo[22.2.1.03,8.08,25]heptacosa-4,12,18,20-tetraene-26,2'-oxirane]-11,17,22-trione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0638 mL | 10.3191 mL | 20.6381 mL | |
| 5 mM | 0.4128 mL | 2.0638 mL | 4.1276 mL | |
| 10 mM | 0.2064 mL | 1.0319 mL | 2.0638 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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