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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 1.8 nM (α1β1εδ, adult) and 3.0 nM (α1β1γδ, fetal)[1]
alphaC-Conotoxin PrXA targets the neuromuscular nicotinic acetylcholine receptor (nAChR) at the motor endplate. It is a competitive antagonist that binds at the interface between the alpha/delta and alpha/gamma subunits, with higher affinity for the alpha/delta subunit interface. It shows high potency against the adult muscle nAChR subtype (alpha1beta1εdelta) with an IC50 of 1.8 nM, and the fetal subtype (alpha1beta1gammadelta) with an IC50 of 3.0 nM. It competes with alpha-bungarotoxin for binding at these sites. |
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| ln Vitro |
In vitro, alphaC-Conotoxin PrXA potently antagonizes mouse muscle nAChRs expressed in Xenopus oocytes or native muscle preparations with IC50 values of 1.8 nM for the adult (alpha1beta1εdelta) and 3.0 nM for the fetal (alpha1beta1gammadelta) subtypes. It is highly specific for neuromuscular nAChRs and shows no activity against other ligand-gated or voltage-gated ion channels tested, including neuronal nAChRs, GABAA receptors, glycine receptors, sodium channels, and calcium channels.
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| ln Vivo |
In vivo, alphaC-Conotoxin PrXA is a potent neurotoxin that causes rapid paralysis and death when administered to mice and fish. When injected intraperitoneally in mice, it produces a flaccid paralysis similar to that seen with snake alpha-neurotoxins, consistent with its action at the neuromuscular junction. The ED50 for paralysis in mice is estimated to be in the low microgram per kilogram range, reflecting its high potency. The toxin is lethal at sufficiently high doses.
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| Enzyme Assay |
The competitive antagonism of alphaC-Conotoxin PrXA at muscle nAChRs is assessed using radioligand competition binding assays. Torpedo or mouse muscle nAChR-rich membranes are incubated with [125I]-labeled alpha-bungarotoxin (alpha-Bgt, 1-2 nM) in the presence of increasing concentrations of alphaC-PrXA (0.001-1000 nM) in binding buffer (20 mM Tris-HCl, pH 7.4, 0.1% BSA). After incubation at room temperature for 60-90 minutes, bound alpha-Bgt is separated by filtration through glass fiber filters pre-soaked in 0.3% polyethylenimine. Non-specific binding is determined in the presence of 1 microM unlabeled alpha-Bgt or 1 mM carbamylcholine. The IC50 for displacement is calculated.
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| Cell Assay |
For functional two-electrode voltage-clamp assays, Xenopus oocytes are co-injected with cRNAs encoding mouse muscle nAChR subunits (alpha1, beta1, ε/gamma, delta). After 2-5 days of expression, oocytes are voltage-clamped at -70 mV. alphaC-PrXA (0.1-100 nM) is pre-applied for 2 minutes, followed by co-application of ACh (10-100 uM). The inhibition of peak ACh-induced current is measured, and IC50 values are calculated from concentration-response curves.
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| Animal Protocol |
For in vivo toxicity assays, alphaC-Conotoxin PrXA is dissolved in saline or PBS and administered via intraperitoneal injection (10-100 uL) to adult male mice (20-25 g). Doses ranging from 0.1-10 ug/kg are tested. Animals are observed for up to 24 hours post-injection for signs of paralysis (loss of righting reflex, respiratory distress) and mortality. The time to onset of paralysis and death is recorded. The median lethal dose (LD50) or median paralytic dose (PD50) is calculated using the up-and-down method or probit analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for alphaC-Conotoxin PrXA are limited. As a 32-amino acid peptide with a single disulfide bond and a molecular weight of approximately 3541 Da, it is not orally bioavailable. It is expected to have a short half-life in circulation due to rapid distribution to the neuromuscular junction and enzymatic degradation. For in vivo studies, it is typically administered intraperitoneally or intravenously. Peptide solutions should be freshly prepared.
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| Toxicity/Toxicokinetics |
Toxicological data for alphaC-Conotoxin PrXA are limited to acute lethality studies in animals. The toxin is highly potent and causes flaccid paralysis and death at low doses in mice. At sub-lethal doses, reversible paralysis may occur without permanent damage. No chronic toxicity studies have been published. Extreme care should be taken when handling this compound as it is a potent neurotoxin. Appropriate safety equipment (gloves, lab coat, eye protection) and protocols should be used.
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| References | |
| Additional Infomation |
alphaC-Conotoxin PrXA is a research-grade neurotoxin and is not approved for clinical use. It defines a new family of conotoxins structurally and genetically unrelated to classical alpha- and alphaA-conotoxins. The peptide sequence is TYGIYDAKPOFSCAGLRGGCVLPONLROKFKE-NH2 (O = 4-trans-hydroxyproline) with a single disulfide bridge linking Cys13 and Cys20. The molecular weight is 3541.06. Store as a lyophilized powder at -20degC, protected from moisture and light.
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| Molecular Formula |
C160H247N43O44S2
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| Molecular Weight |
3541.06
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| Appearance |
White to off-white solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO :~100 mg/mL (~28.24 mM)
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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 | 0.2824 mL | 1.4120 mL | 2.8240 mL | |
| 5 mM | 0.0565 mL | 0.2824 mL | 0.5648 mL | |
| 10 mM | 0.0282 mL | 0.1412 mL | 0.2824 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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