| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
CFTR activator 2 targets the mutant cystic fibrosis transmembrane conductance regulator (mutant-CFTR), a chloride channel protein. CFTR is a member of the ATP-binding cassette (ABC) transporter family. Mutations in the CFTR gene, such as deltaF508 (the most common mutation), lead to misfolding, impaired trafficking, and/or reduced channel gating, resulting in cystic fibrosis. CFTR activator 2 (WAY-326769) is a small molecule activator that enhances the activity of mutant-CFTR, particularly by increasing channel gating (open probability). It improves chloride transport across the apical membrane of epithelial cells, thereby reducing the symptoms of CF.
|
|---|---|
| ln Vitro |
In vitro, CFTR activator 2 (WAY-326769) is an activator of mutant cystic fibrosis transmembrane conductance regulator (mutant-CFTR). It enhances the chloride channel activity of CFTR mutants, including deltaF508-CFTR, in cell-based assays. The compound increases the open probability of the channel, restoring chloride transport in CF airway epithelial cells. Specific EC₅0 values are not provided. The compound is a research tool for studying CFTR biology and for developing CFTR modulator therapies.
|
| ln Vivo |
In vivo, CFTR activator 2 is a research-grade compound and is not an approved drug. It is used to study the effects of CFTR activation in animal models of cystic fibrosis, such as CFTR-/- mice or mice expressing the deltaF508 mutation. The compound can be administered orally or intraperitoneally to assess its effects on CFTR function and disease pathology. No specific in vivo efficacy data is provided.
|
| Enzyme Assay |
The in vitro CFTR chloride channel activity can be measured by patch-clamp electrophysiology or by using a fluorescent membrane potential dye. CFTR-expressing cells (e.g., CHO, BHK, or primary airway epithelial cells) are seeded in 96-well black plates (2×10⁴ cells/well). They are pre-incubated with CFTR activator 2 (0.1-100 uM) for 5-30 min at 37degC. A membrane potential-sensitive dye (e.g., bis-oxonol, FLIPR Membrane Potential dye) is added, and fluorescence is measured at λex 530 nm, λem 570 nm. Forskolin (10-20 uM) is used as a positive control. The change in fluorescence upon addition of an iodide gradient reflects CFTR activity. EC₅0 is calculated.
|
| Cell Assay |
For cell-based assays, Fisher rat thyroid (FRT) cells stably expressing deltaF508-CFTR are seeded in 96-well plates (2×10⁴ cells/well). Cells are grown for 48 h, then incubated at 27degC for 24-48 h to rescue deltaF508-CFTR to the plasma membrane. CFTR activator 2 (0.1-100 uM) is added for 15-60 min. CFTR-mediated chloride transport is measured using a halide-sensitive fluorescent dye (MQAE or YFP-H148Q/I152L). The increase in fluorescence upon iodide (I-) addition is measured. The EC₅0 is calculated. Cytotoxicity is assessed by MTT assay.
|
| Animal Protocol |
In vivo efficacy can be evaluated in a mouse model of cystic fibrosis. CFTR-/- mice or mice expressing the deltaF508 mutation (e.g., CFTRdeltaF508/deltaF508) are used. CFTR activator 2 is formulated in 10% DMSO + 5% Tween 80 + 85% saline or in 0.5% methylcellulose and administered orally (PO) at doses of 10-100 mg/kg once daily for 14-28 days. Control groups receive vehicle alone. Intestinal potential difference (PD) is measured as a readout of CFTR function. Sweat chloride levels are measured by pilocarpine iontophoresis. The compound is expected to normalize intestinal PD and reduce sweat chloride levels.
|
| ADME/Pharmacokinetics |
No PK data for CFTR activator 2 is available. As a small molecule (MW 441.52), it is expected to have moderate oral bioavailability. Solubility: DMSO: 125 mg/mL (283.11 mM, need ultrasonic). For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline or in 0.5% methylcellulose. For research use, it is stored as a powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month, protect from light.
|
| Toxicity/Toxicokinetics |
For CFTR activator 2, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: at -20degC, sealed, protect from light.
|
| References | |
| Additional Infomation |
CFTR activator 2 (WAY-326769; CAS# 871700-29-7) is a research-grade mutant CFTR activator. It is not an FDA-approved drug (CFTR modulators such as ivacaftor, lumacaftor, tezacaftor, and elexacaftor are approved). It is used to study CFTR gating and for research into CF therapies. For research use only, not for diagnostic or therapeutic applications.
|
| Molecular Formula |
C27H27N3O3
|
|---|---|
| Molecular Weight |
441.52
|
| CAS # |
871700-29-7
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
732.0±60.0 °C at 760 mmHg
|
| Flash Point |
396.5±32.9 °C
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
| Index of Refraction |
1.668
|
| LogP |
4.22
|
| SMILES |
N1C2=C(C=CC=C2)C(CC(N(C(C2=CC=C(C)C=C2)C(NC2=CC=C(OC)C=C2)=O)C)=O)=C1
|
| Synonyms |
WAY-326769
|
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~125 mg/mL (~283.11 mM; with ultrasonication)
|
|---|---|
| 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 | 2.2649 mL | 11.3245 mL | 22.6490 mL | |
| 5 mM | 0.4530 mL | 2.2649 mL | 4.5298 mL | |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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
