| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Posenacaftor sodium specifically targets the cystic fibrosis transmembrane conductance regulator (CFTR) protein. It is a CFTR modulator, functioning as a protein corrector.. It is designed to bind to the defective CFTR protein, correct its misfolding, and facilitate its proper trafficking to the cell surface. This mechanism classifies it as a CFTR corrector..
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| ln Vitro |
Posenacaftor is a CFTR corrector; correctors are proteins that are faulty in CFTR that are intended to be repaired and functionally restored. After that, the modified CFTR travels to the cell surface where it serves as a chloride channel to assist keep the fluid balance in the airways in the right position [2].
In vitro, Posenacaftor sodium is a newly developed p.Phe508del-CFTR corrector. It demonstrates an EC50 of 0.52 uM, as measured by the HS-YFP (halide-sensitive yellow fluorescent protein) quenching rate.. At 1 and 3 uM concentrations, it shows greater efficacy in rescuing p.Phe508del-CFTR function compared to VX-661 at 5 uM.. In combination with other correctors like ABBV-2222 or VX-809, it shows greater correction effects, but not with VX-445.. |
| ln Vivo |
Specific in vivo activity data for Posenacaftor sodium has not been detailed in the provided search results. However, as a CFTR corrector intended for the treatment of cystic fibrosis, its in vivo efficacy would be evaluated in animal models of the disease (such as CFTR knockout mice or ferrets) by measuring improvements in chloride transport and a reduction in disease pathology. It is currently a research candidate.
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| Enzyme Assay |
Due to its cellular mechanism, standard in vitro binding assays may not directly apply. The primary method to assess its effect is a functional cellular assay to measure CFTR correction. However, a CFTR binding assay can be performed using a radiolabeled CFTR modulator. For Posenacaftor sodium, the correction activity is measured using a cell-based halide-sensitive yellow fluorescent protein (HS-YFP) assay. This technique quantifies the rate of halide influx into cells, which is directly proportional to the activity of CFTR chloride channels on the cell surface..
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| Cell Assay |
The standard in vitro cellular assay for CFTR correctors involves using Fisher rat thyroid (FRT) cells or primary human bronchial epithelial (HBE) cells expressing the F508del-CFTR mutation. Cells are treated with Posenacaftor sodium (PTI-801) for 24-48 hours to allow for protein correction and trafficking. After incubation, CFTR function is measured using a fluorescence-based plate reader in a halide-sensitive yellow fluorescent protein (HS-YFP) quenching assay. Cells are exposed to an iodide gradient, and the rate of fluorescence decay, reflecting CFTR-mediated halide influx, is quantified to determine EC50 values..
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| Animal Protocol |
In vivo protocols for evaluating CFTR correctors like PTI-801 typically involve CFTR knockout or F508del-CFTR mouse models. Mice are administered Posenacaftor sodium via oral gavage at doses ranging from 10-60 mg/kg daily for 1-4 weeks. Efficacy is assessed by measuring CFTR-dependent chloride secretion in the intestine using Ussing chamber technology (short-circuit current measurement). Improvements in survival rate, body weight, and histological analysis of lung and intestinal tissues are also evaluated. Pharmacodynamic assessments include measuring CFTR protein levels and localization in tissue sections via immunofluorescence and Western blotting.
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| ADME/Pharmacokinetics |
As a CFTR protein corrector, Posenacaftor sodium is intended for oral administration. Detailed pharmacokinetic parameters have not been published, but based on its structure, it is expected to be absorbed and metabolized by the liver. For research purposes, it is solubilized in DMSO and can be administered in vivo using formulations like 10% DMSO/40% PEG300/5% Tween-80/45% saline. A stock solution of 200 mg/mL in DMSO is reported..
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| Toxicity/Toxicokinetics |
Specific toxicological data for Posenacaftor sodium is not available. Standard safety screening for CFTR modulators would include in vitro cytotoxicity assays (e.g., MTT assay on FRT or HBE cells) and hERG channel inhibition testing for potential cardiac toxicity. In vivo, a 14-day repeat-dose oral toxicity study in rats would be performed to determine the maximum tolerated dose (MTD) and monitor for target organ toxicity, particularly effects on the liver and gastrointestinal tract.
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| References | |
| Additional Infomation |
Posenacaftor (PTI-801) is an investigational CFTR corrector that has been in clinical development for the treatment of cystic fibrosis (CF). It is classified as a next-generation CFTR corrector developed by Proteostasis Therapeutics. Clinical trials have investigated its safety and efficacy alone and in combination with other CFTR modulators (e.g., PTI-808). As of current information, its development status may have been discontinued or deprioritized, though it remains a valuable research tool for CFTR biology and drug discovery.
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| Molecular Formula |
C27H26NNAO5
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|---|---|
| Molecular Weight |
467.49
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| Exact Mass |
467.17
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| CAS # |
2095064-06-3
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| Related CAS # |
Posenacaftor;2095064-05-2
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| PubChem CID |
135350953
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| Appearance |
Yellow to brown solid powder
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| Hydrogen Bond Donor Count |
0
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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 |
688
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C2C(=C(C=C1)O[C@H](C)C3CCOCC3)C(=CC(=N2)C4=C(C5=CC=CC=C5O4)C)C(=O)[O-].[Na+]
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| InChi Key |
FIMNRWQYZVDFTK-UNTBIKODSA-M
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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);/q;+1/p-1/t17-;/m1./s1
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| Chemical Name |
sodium;8-methyl-2-(3-methyl-1-benzofuran-2-yl)-5-[(1R)-1-(oxan-4-yl)ethoxy]quinoline-4-carboxylate
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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: 200 mg/mL (427.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (10.70 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: 5 mg/mL (10.70 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 50.0 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 | 2.1391 mL | 10.6954 mL | 21.3908 mL | |
| 5 mM | 0.4278 mL | 2.1391 mL | 4.2782 mL | |
| 10 mM | 0.2139 mL | 1.0695 mL | 2.1391 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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