| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: CFTR[1]
(R)-Posenacaftor sodium specifically targets the cystic fibrosis transmembrane conductance regulator (CFTR) protein. As a CFTR corrector, its mechanism involves binding to the misfolded CFTR protein to facilitate its proper folding and trafficking to the cell surface. This allows the CFTR protein to be inserted into the plasma membrane, where it can function as a chloride channel to regulate ion and fluid balance.. |
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| ln Vitro |
The autosomal recessive illness known as cystic fibrosis (CF) is brought on by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)[1]. The CFTR chloride channel is typically found at the apical membrane of epithelial cells and is controlled by cAMP. A malfunctioning and misfolded CFTR protein is produced when the CFTR gene is mutated, which hinders the movement of ions into and out of cells[1]. Posenacaftor is a CFTR corrector; correctors are made to correct and restore the CFTR protein's malfunction. After then, the modified CFTR travels to the cell surface, where it serves as a chloride channel and aids in preserving the proper fluid balance in the airways[2].
Specific in vitro activity data for (R)-Posenacaftor sodium, such as an EC50 value, is not detailed in the provided search results. The parent compound Posenacaftor (PTI-801) is a CFTR corrector with an EC50 of 0.52 uM for the p.Phe508del-CFTR mutation. As the R-enantiomer, (R)-Posenacaftor sodium may exhibit a similar or distinct potency profile, but this specific data was not found. |
| ln Vivo |
Specific in vivo activity data for (R)-Posenacaftor sodium has not been detailed in the provided search results. As a CFTR corrector, its in vivo efficacy would be evaluated in a relevant animal model of cystic fibrosis (CF). Using a CFTR knockout mouse expressing the human F508del-CFTR mutation, the compound would be administered orally to assess its ability to rescue CFTR function. Efficacy would be measured by CFTR-dependent chloride secretion in the intestine via Ussing chamber or by nasal potential difference (NPD).
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| Enzyme Assay |
There is no specific cell-free binding protocol for (R)-Posenacaftor sodium. As a CFTR corrector, its activity is not measured by binding to an isolated enzyme. The most direct cell-free method would be an ATPase activity assay using purified CFTR protein reconstituted into lipid bilayers. The compound's ability to stimulate the ATPase activity of the purified protein can be measured by quantifying the release of inorganic phosphate (Pi) from ATP hydrolysis. However, this method is complex and not routinely used. The primary assessment is via cellular assays.
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| Cell Assay |
The standard in vitro cellular assay for evaluating a CFTR corrector like (R)-Posenacaftor sodium uses Fischer rat thyroid (FRT) cells or primary human bronchial epithelial (HBE) cells that stably express the F508del-CFTR mutation. The cells are seeded in 96-well plates and allowed to reach confluency. The cells are then treated with varying concentrations of (R)-Posenacaftor sodium (from 0.001 uM to 10 uM) for 24-48 hours to allow for protein correction and trafficking to the cell surface. After treatment, CFTR function is measured using a fluorescence-based plate reader in a halide-sensitive yellow fluorescent protein (HS-YFP) quenching assay. The cells are exposed to an iodide gradient, and the rate of fluorescence decay is recorded. The EC50 value is calculated from the dose-response curve.
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| Animal Protocol |
A standard in vivo protocol for a CFTR corrector like (R)-Posenacaftor sodium would involve a CFTR knockout mouse model (e.g., Cftrtm1Unc) that has been transgenically engineered to express the human F508del-CFTR mutation. The compound is formulated in a vehicle such as 5% DMSO/40% PEG300/5% Tween-80/45% saline and administered by oral gavage at doses ranging from 10-50 mg/kg daily for 1-4 weeks. The primary efficacy endpoint is the measurement of CFTR-dependent chloride secretion in the intestinal tract using Ussing chamber technology (short-circuit current). Secondary endpoints include improvement in weight gain, survival rates, and histological analysis of lung and intestinal tissues.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for (R)-Posenacaftor sodium is not provided. As a small molecule with a molecular weight of 467.49 g/mol, it is likely designed for oral administration.. For research purposes, it is solubilized in DMSO for in vitro work and can be formulated for in vivo administration. The parent compound Posenacaftor is a p.Phe508del-CFTR corrector. (R)-Posenacaftor sodium is the R-enantiomer, which may have distinct PK properties such as a different half-life or metabolic clearance rate compared to the racemate or the S-enantiomer.
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| Toxicity/Toxicokinetics |
Specific toxicological data for (R)-Posenacaftor sodium is not available. Standard safety screening for a CFTR modulator would include an in vitro cytotoxicity assay (e.g., MTT) on primary human cells to determine the maximum non-toxic concentration. A hERG (human Ether-à-go-go-Related Gene) channel inhibition test would be performed to assess the potential for QT interval prolongation and cardiotoxicity. In vivo, a 7- to 14-day repeat-dose oral toxicity study in rats would be required to determine the Maximum Tolerated Dose (MTD) and to identify any target organ toxicity, particularly in the liver (due to potential drug-induced liver injury) and the gastrointestinal tract (due to the mechanism of action).
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| References | |
| Additional Infomation |
(R)-Posenacaftor sodium is a research-grade chemical and is not approved for clinical use. It is the R-enantiomer of Posenacaftor (PTI-801), which was a CFTR corrector candidate in clinical development for the treatment of cystic fibrosis (CF). (R)-Posenacaftor sodium is a valuable tool for research into the stereospecific effects of CFTR modulators, allowing scientists to study how different molecular configurations interact with the CFTR protein. It is for research use only.
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| Molecular Formula |
C27H28NNAO5
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|---|---|
| Molecular Weight |
469.504698753357
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| Exact Mass |
468.178
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| CAS # |
2095064-09-6
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| PubChem CID |
168012957
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| Appearance |
Yellow to brown solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
681
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C1=CC=C(C)C2N=C(C3OC4=CC=CC=C4C=3C)C=C(C(=O)O)C1=2)[C@H](C1CCOCC1)C.[NaH]
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| InChi Key |
GSYMTYPDLBWOIU-LMOVPXPDSA-N
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| InChi Code |
InChI=1S/C27H27NO5.Na/c1-15-8-9-23(32-17(3)18-10-12-31-13-11-18)24-20(27(29)30)14-21(28-25(15)24)26-16(2)19-6-4-5-7-22(19)33-26;/h4-9,14,17-18H,10-13H2,1-3H3,(H,29,30);/t17-;/m0./s1
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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, avoid exposure to moisture. |
| 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: 38.33 mg/mL (81.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.83 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 38.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 3.83 mg/mL (8.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 38.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1299 mL | 10.6496 mL | 21.2993 mL | |
| 5 mM | 0.4260 mL | 2.1299 mL | 4.2599 mL | |
| 10 mM | 0.2130 mL | 1.0650 mL | 2.1299 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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