| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 0.75 μM (α3β4 nAChR; in Xenopus oocytes)[1]
alpha-Conotoxin AuIB selectively targets the alpha3beta4 subunit combination of the nicotinic acetylcholine receptor (nAChR). It blocks this receptor with >100-fold higher potency than other subunit combinations including alpha2beta2, alpha2beta4, alpha3beta2, alpha4beta2, alpha4beta4, and alpha1beta1gammadelta. Additionally, it inhibits the GABAB receptor (GABABR)-coupled N-type calcium channel (CaV2.2) at higher concentrations (IC50 ~4.5 microM), representing a secondary mechanism contributing to its analgesic effects. |
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| ln Vitro |
In vitro, alpha-Conotoxin AuIB (0.75 microM) blocks alpha3beta4 nAChRs expressed in Xenopus oocytes with an IC50 of 0.75 microM. At 1-5 microM, it blocks 20-35% of nicotine-stimulated norepinephrine release from rat hippocampal synaptosomes without affecting dopamine release. In rat parasympathetic neurons, it blocks approximately 75% of nicotine-induced currents. It also inhibits GABABR-coupled N-type calcium channels with an IC50 of approximately 4.5 microM.
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| ln Vivo |
In vivo, alpha-Conotoxin AuIB (10 nM-1 microM, intrathecal) produces a dose-dependent reversal of mechanical allodynia in neuropathic pain models, with a maximal reversal of 88% at 1 microM in rats. Intrathecal administration (120 pmol) reduces mechanical allodynia for up to 6 hours without significant side effects. The analgesic activity is mediated through both alpha3beta4 nAChR antagonism and inhibition of the GABABR/CaV2.2 pathway, which provides a new paradigm for pain relief.
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| Enzyme Assay |
The in vitro binding affinity of alpha-Conotoxin AuIB to nAChR subtypes is assessed using radioligand binding assays. Membranes prepared from cells expressing specific nAChR subtypes are incubated with [125I]-labeled alpha-bungarotoxin or [3H]-epibatidine in the presence of increasing concentrations of AuIB (0.01-100 microM). Non-specific binding is determined using excess cold competitor (e.g., 10 microM nicotine). After incubation at room temperature for 60-90 minutes, bound radioligand is separated by filtration, and radioactivity is counted to calculate Ki values.
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| Cell Assay |
For functional cell-based assays, Xenopus laevis oocytes are injected with cRNA encoding human or rat nAChR subunits (alpha3 and beta4). After 2-5 days of expression, two-electrode voltage-clamp recordings are performed at a holding potential of -70 mV. Varying concentrations of alpha-Conotoxin AuIB (0.001-10 microM) are pre-incubated for 2 minutes, followed by application of ACh (10-100 microM). The peak current inhibition is measured and IC50 values are calculated using dose-response curves. Oocytes are maintained in ND96 solution at room temperature.
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| Animal Protocol |
For in vivo analgesic studies, neuropathic pain is induced in adult male Sprague-Dawley rats by partial sciatic nerve ligation (Seltzer model) or spinal nerve ligation (Chung model). After confirmation of mechanical allodynia (day 7-14 post-surgery), alpha-Conotoxin AuIB is dissolved in artificial cerebrospinal fluid (aCSF) and administered intrathecally via a lumbar puncture (10-20 microL volume) at doses ranging from 0.1-300 pmol/rat. Mechanical allodynia is assessed using von Frey filaments at 0.5, 1, 2, 4, and 6 hours post-administration. Motor function is evaluated by the rotarod test to exclude non-specific effects.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for alpha-Conotoxin AuIB are limited. As a 16-amino acid peptide with a molecular weight of approximately 1686.79 Da, it is not orally bioavailable and is typically administered by intrathecal or local routes to achieve CNS effects. The peptide is stable in aqueous solution at concentrations above 100 mg/mL and should be stored as a lyophilized powder at -20degC. In vivo half-life in CSF is likely short due to rapid enzymatic degradation.
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| Toxicity/Toxicokinetics |
Published toxicology data for alpha-Conotoxin AuIB are limited. In animal studies at analgesic doses (up to 1 microM intrathecal), no significant motor impairment or other overt side effects have been reported. In cell-based assays at concentrations used for nAChR blockade (0.75-5 microM), no direct cytotoxicity has been observed. Comprehensive toxicological profiling has not been publicly released.
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| References | |
| Additional Infomation |
alpha-Conotoxin AuIB TFA is a research-grade compound and is not approved for clinical use. It serves as a selective pharmacological tool for studying alpha3beta4 nAChR function in autonomic ganglia, neurotransmitter release, and pain pathways. Its unique ability to also inhibit GABABR-coupled calcium channels makes it valuable for studying neuropathic pain mechanisms. The compound has the sequence GCCSYPPCFATNPDC-NH2 with disulfide bridges between Cys2-Cys8 and Cys3-Cys15, and a molecular weight of 1686.79. Store at -20degC as a lyophilized powder.
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| Molecular Formula |
C67H90F3N17O23S4
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| Molecular Weight |
1686.79
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| Appearance |
Typically exists as solid at room temperature
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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) |
H2O :~110 mg/mL (~65.21 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 | 0.5928 mL | 2.9642 mL | 5.9284 mL | |
| 5 mM | 0.1186 mL | 0.5928 mL | 1.1857 mL | |
| 10 mM | 0.0593 mL | 0.2964 mL | 0.5928 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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