| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
The primary molecular targets of Verruculogen are calcium-activated potassium (K⁺) channels, specifically the large-conductance (maxi-K) channels. Verruculogen acts as a potent blocker of these channels, inhibiting the amplitude of Ca²⁺-activated K⁺ currents. It enhances the binding of charybdotoxin (ChTX), a known maxi-K channel blocker, to the channel with a K₁/₂ value of 170 nM, indicating a strong allosteric interaction. This inhibition of K⁺ channels disrupts cellular ion homeostasis, affecting membrane potential and neuronal excitability. The compound also functions as an inhibitor of the mammalian cell cycle, specifically blocking the M phase. Its ability to inhibit cell cycle progression is likely related to its effects on K⁺ channels and other cellular targets. Additionally, Verruculogen has been reported to induce toll-like receptor (TLR) signaling in vitro, suggesting a role in modulating immune responses.
|
|---|---|
| ln Vitro |
Verruculogen demonstrates potent in vitro activity against various cellular targets. It inhibits Ca²⁺-activated K⁺ currents, with a significant effect on maxi-K channels. In cell-based assays, it has shown cytotoxicity against human HT-29 colon cancer cells with an IC₅₀ of 20 μM. This cytotoxic effect is likely related to its ability to block K⁺ channels and inhibit cell cycle progression. The compound also exhibits activity as an M-phase inhibitor of the mammalian cell cycle. Its tremorgenic activity is a hallmark of its in vitro and in vivo effects. The compound is a complex molecule with a high degree of structural complexity, as indicated by its 999 complexity score. Its physicochemical properties, including a LogP of 2.6 and a density of 1.5 g/cm³, are well-defined.
|
| ln Vivo |
In vivo, Verruculogen is a potent tremorgenic mycotoxin that causes severe tremors in infected animals. Its toxic effects are primarily neurological, leading to muscle tremors, ataxia, and convulsions. The mechanism of action involves the blockade of Ca²⁺-activated K⁺ channels in the central nervous system, which disrupts neuronal signaling and leads to hyperexcitability. It is produced by fungi such as Penicillium and Aspergillus and can contaminate food and feed, posing a significant health risk to humans and animals. Its potent in vivo toxicity makes it a compound of interest in the study of mycotoxin poisoning and food safety. The compound's ability to cross the blood-brain barrier is a key factor in its neurological effects.
|
| Enzyme Assay |
In vitro assays for Verruculogen are primarily focused on studying its effects on ion channels and cell cycle progression. For ion channel studies, patch-clamp electrophysiology is the gold standard. In this assay, cells (e.g., CHO cells expressing maxi-K channels) are patch-clamped, and the effect of Verruculogen on K⁺ currents is measured. The compound is applied to the bath solution at various concentrations, and the inhibition of the current amplitude is recorded. For cell cycle studies, cells are treated with Verruculogen, and the cell cycle distribution is analyzed by flow cytometry after staining with propidium iodide. The compound's ability to arrest cells in the M phase can be quantified. These assays provide a detailed understanding of the compound's mechanism of action.
|
| Cell Assay |
In vitro cell-based assays for Verruculogen are used to study its cytotoxic and cell cycle effects. A common assay involves treating cancer cell lines (e.g., HT-29) with the compound for 24-72 hours. Cell viability is then measured using an MTT or CellTiter-Glo assay. The IC₅₀, the concentration that inhibits 50% of cell growth, is calculated. Apoptosis can be assessed by measuring caspase-3/7 activity or by using Annexin V staining and flow cytometry. The compound's effect on cell cycle progression is analyzed by flow cytometry after staining with propidium iodide. These assays are essential for characterizing the compound's anti-proliferative activity and its potential as a lead compound for cancer research.
|
| Animal Protocol |
In vivo animal studies for Verruculogen are typically conducted to study its toxic effects. A common model is the administration of the compound to rodents (e.g., mice or rats) via intraperitoneal or oral routes. The animals are monitored for the onset and severity of tremors, ataxia, and other neurological symptoms. The dose-response relationship and the time course of the toxic effects are determined. Histopathological analysis of brain tissue can be performed to assess neuronal damage. These studies are crucial for understanding the mechanism of tremorgenic mycotoxin poisoning and for developing strategies to mitigate its effects.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Verruculogen are characterized by its rapid absorption and distribution, particularly to the central nervous system. Its ability to cross the blood-brain barrier is a key factor in its tremorgenic effects. The compound is metabolized in the liver and excreted in the bile and urine. Its half-life in the body is relatively short, but its potent effects can be observed at very low concentrations. The compound is soluble in DMSO and can be formulated for in vivo administration. It should be stored as a powder at -20°C for long-term stability.
|
| Toxicity/Toxicokinetics |
The toxicological profile of Verruculogen is dominated by its potent neurotoxicity. It is a severe tremorgenic mycotoxin that causes muscle tremors, ataxia, and convulsions in animals. Its primary mechanism of action is the blockade of Ca²⁺-activated K⁺ channels in the central nervous system. At high doses, it can be lethal. The compound is also a potent inhibitor of the cell cycle, which may contribute to its cytotoxic effects. It is classified as a hazardous compound and should be handled with extreme caution. Standard safety protocols for handling mycotoxins should be followed, including the use of personal protective equipment and working in a fume hood. The compound is for research use only.
|
| References |
|
| Additional Infomation |
Verruculogen is an organic heterohexacyclic compound belonging to the class of fungal toxins and indole alkaloids isolated from Penicillium and Aspergillus fungi. It possesses multiple functions, including acting as a fungal toxin, potassium channel blocker, GABA regulator, and metabolite of Aspergillus and Penicillium. It is an indole alkaloid, diol, aromatic ether, organic peroxide, and organic heterohexacyclic compound. Verruculogen has been reported in Talaromyces verruculosus, Aspergillus fischeri, and other organisms with relevant data.
Verruculogen is a tremorgenic indole alkaloid mycotoxin produced by Penicillium and Aspergillus species. It is an inhibitor of Ca²⁺-activated K⁺ channels and an M-phase inhibitor of the mammalian cell cycle. It is a member of the fumitremorgin-type diketopiperazine family. The compound is known by its CAS number 12771-72-1 and has a molecular formula of C₂₇H₃₃N₃O₇. It is intended for research use only and is not for human therapeutic or diagnostic use. |
| Molecular Formula |
C27H33N3O7
|
|---|---|
| Molecular Weight |
511.5668
|
| Exact Mass |
511.231
|
| CAS # |
12771-72-1
|
| PubChem CID |
13887805
|
| Appearance |
White to light brown solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
738.4±60.0 °C at 760 mmHg
|
| Melting Point |
233ºC
|
| Flash Point |
400.3±32.9 °C
|
| Vapour Pressure |
0.0±2.6 mmHg at 25°C
|
| Index of Refraction |
1.691
|
| LogP |
2.6
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
37
|
| Complexity |
999
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
CC(=C[C@@H]1N2C3=C(C=CC(=C3)OC)C4=C2[C@H](CC(OO1)(C)C)N5C(=O)[C@@H]6CCCN6C(=O)[C@@]5([C@H]4O)O)C
|
| InChi Key |
LRXYHMMJJCTUMY-GWXUGYLUSA-N
|
| InChi Code |
InChI=1S/C27H33N3O7/c1-14(2)11-20-29-18-12-15(35-5)8-9-16(18)21-22(29)19(13-26(3,4)37-36-20)30-24(32)17-7-6-10-28(17)25(33)27(30,34)23(21)31/h8-9,11-12,17,19-20,23,31,34H,6-7,10,13H2,1-5H3/t17-,19-,20+,23-,27+/m0/s1
|
| Chemical Name |
(9R,14S,17S,23R,24S)-23,24-dihydroxy-5-methoxy-12,12-dimethyl-9-(2-methylprop-1-enyl)-10,11-dioxa-8,15,21-triazahexacyclo[12.10.1.02,7.08,25.015,23.017,21]pentacosa-1(25),2(7),3,5-tetraene-16,22-dione
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 1.9548 mL | 9.7738 mL | 19.5477 mL | |
| 5 mM | 0.3910 mL | 1.9548 mL | 3.9095 mL | |
| 10 mM | 0.1955 mL | 0.9774 mL | 1.9548 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
