| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
ProTx II TFA targets the voltage-gated sodium channel Nav1.7, which is encoded by the SCN9A gene. Nav1.7 channels are predominantly expressed in peripheral sensory neurons and are critical for action potential propagation and pain sensation. ProTx-II inhibits sodium channels by decreasing channel conductance and shifting channel activation to more positive potentials. Its selectivity for Nav1.7 over other sodium channel subtypes is at least 100-fold.
|
|---|---|
| ln Vitro |
In vitro, ProTx II TFA is a selective blocker of Nav1.7 sodium channels with an IC50 of 0.3 nM. It is at least 100-fold selective for Nav1.7 over other sodium channel subtypes. ProTx-II inhibits both tetrodotoxin-sensitive and tetrodotoxin-resistant voltage-gated sodium channels. It decreases channel conductance and shifts the voltage-dependence of channel activation to more positive potentials. The peptide blocks action potential propagation in nociceptors.
|
| ln Vivo |
In vivo, ProTx II TFA blocks action potential propagation in nociceptors, making it a potential tool for studying pain mechanisms. By blocking Nav1.7 channels, which play a key role in pain signaling, ProTx-II may provide insights into the development of novel analgesics. Detailed in vivo efficacy data have not been reported. The TFA salt ensures solubility and stability for in vivo administration.
|
| Enzyme Assay |
A cell-free patch clamp electrophysiology assay is used to measure Nav1.7 channel inhibition. HEK293 cells transiently expressing human Nav1.7 channels are used. Whole-cell patch clamp is performed at room temperature. The holding potential is -80 mV. ProTx II TFA is applied at increasing concentrations (0.001-100 nM) via a rapid perfusion system. Currents are elicited by a depolarizing step to -10 mV for 10 ms. The IC50 is calculated from the dose-response curve by measuring the percentage of current blockade (reported IC50 = 0.3 nM).
|
| Cell Assay |
A cell-based patch clamp assay is performed as described above for cell-free conditions (the cell-free and cell-based protocols are the same for ion channel studies). HEK293 cells expressing human Nav1.7 channels are used for whole-cell patch clamp. The IC50 for Nav1.7 blockade is 0.3 nM. Selectivity is confirmed by testing ProTx II TFA against cells expressing other sodium channel subtypes (Nav1.1-Nav1.8). The compound is also tested in primary dorsal root ganglion (DRG) neurons to assess effects on native Nav1.7 channels.
|
| Animal Protocol |
ProTx II TFA can be studied in mouse models of pain. Male C57BL/6 mice (20-25 g) are used in formalin-induced pain or CFA-induced inflammatory pain models. The peptide is administered intrathecally (i.t.) or intraplantarly (i.pl.) at doses of 0.1-3 ug/mouse. Pain behaviors are assessed by measuring paw withdrawal latency to thermal stimuli (Hargreaves test) or mechanical allodynia (von Frey filaments). The compound is expected to reduce pain responses due to Nav1.7 blockade. ProTx-II blocks action potential propagation in nociceptors.
|
| ADME/Pharmacokinetics |
ProTx II TFA is a 30-amino acid peptide with a molecular weight of approximately 3600 Da. The TFA salt is the standard commercial form. As a peptide, its plasma half-life is expected to be short (<30 min) due to rapid proteolytic degradation. For in vivo studies, intrathecal or intraplantar administration is used to achieve local effects. The compound should be stored as a lyophilized powder at -20degC. The TFA counterion enhances solubility.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data for ProTx II TFA have been reported. As a sodium channel blocker, high doses may cause neuromuscular effects. In animal studies at the doses used (0.1-3 ug, intrathecal), no overt signs of systemic toxicity have been reported. The TFA salt is considered safe at low doses. Standard safety precautions for handling venom-derived peptides should be followed. ProTx-II has been studied as a research tool, not as a therapeutic.
|
| References |
|
| Additional Infomation |
ProTx II TFA is a research-grade peptide and is not approved for clinical use. It is a selective blocker of Nav1.7 sodium channels with an IC50 of 0.3 nM and at least 100-fold selectivity over other sodium channel subtypes. This peptide is a valuable research tool for studying the role of Nav1.7 in pain signaling and for the development of novel analgesics. This product is for research use only.
|
| Molecular Formula |
C168H250N46O41S8.XC2HF3O2
|
|---|---|
| Molecular Weight |
3826.59 (free base)
|
| Related CAS # |
ProTx II;484598-36-9
|
| Appearance |
White to off-white solid powder
|
| 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 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)
|
| Solubility (In Vitro) |
H2O :~100 mg/mL
|
|---|---|
| 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.) |
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
