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Formula | C24H28N2O3 |
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Molecular Weight | 392.49 | CAS No. | 873054-44-5 | ||||
Solubility (25°C)* | In vitro | DMSO | 78 mg/mL (198.73 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
In vivo (Add solvents to the product individually and in order) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Ivacaftor (VX-770) is a selective potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM in fisher rat thyroid cells, respectively. | ||||
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In vitro | Ivacaftor (10 μM) significantly increases the forskolin-stimulated Cl- secretion (IT) by ~4-fold with an EC50 of 100 nM in the recombinant Fisher rat thyroid (FRT) cells expressing G551D gating mutation of CFTR, and by ~6-fold with an EC50 of 25 nM in the recombinant cells expressing temperature-corrected F508del processing mutation of CFTR. Consistent with the increases in the forskolin-stimulated IT, Ivacaftor (10 μM) increases the open probability (Po) of G551D-, F508del-, and wild-type CFTR by ~6-fold, ~5-fold and ~2-fold, respectively, indicating that Ivacaftor acts directly on CFTR to increase its gating activity. In primary cultured human CF bronchial epithelia (HBE) carrying the G551D and F508del CFTR mutations, Ivacaftor (10 μM) potently increases the forskolin-stimulated IT by ~10-fold from 5% to a maximum level of 48% of that measured in non-CF HBE, with an EC50 of 236 nM displaying ~70-fold more potency compared with the commonly used CFTR potentiator genistein, which has an EC50 of 16 μM. In HBE with F508del homozygous CFTR, Ivacaftor causes a significant increase in the forskolin-stimulated IT with an EC50 of 22 nM, to a less extent from 4% to 16% of non-CF HBE compared with the effect in G551D/F508del HBE. Due to CFTR potentiation, Ivacaftor inhibits excessive ENaC-mediated Na+ and fluid absorption with an IC50 of 43 nM, and decreases the response, resulting in an increase in the surface fluid and cilia beat frequency (CBF) in G551D/F508del HBE. [1] |
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Features | The first potent and orally available CFTR potentiator to enter human clinical trials. |
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Data from [Data independently produced by Sci Transl Med, 2014, 6(246), 246ra96]
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Data from [Data independently produced by , , Hepatology, 2018, 67(3):972-988]
FGF receptors mediate cellular senescence in the cystic fibrosis airway epithelium [ JCI Insight, 2024, 9(15)e174888] | PubMed: 38916962 |
Septin-dependent defense mechanisms against Pseudomonas aeruginosa are stalled in cystic fibrosis bronchial epithelial cells [ Eur J Cell Biol, 2024, 103(2):151416] | PubMed: 38636185 |
Comprehensive Assessment of CFTR Modulators' Therapeutic Efficiency for N1303K Variant [ Int J Mol Sci, 2024, 25(5)2770] | PubMed: 38474016 |
PTI-801 (posenacaftor) shares a common mechanism with VX-445 (elexacaftor) to rescue p.Phe508del-CFTR [ Eur J Pharmacol, 2024, 967:176390] | PubMed: 38336013 |
Localization and function of humanized F508del-CFTR in mouse intestine following activation of serum glucocorticoid kinase 1 and Trikafta [ Eur J Pharmacol, 2024, 978:176771] | PubMed: 38925289 |
Reduced sialylation of airway mucin impairs mucus transport by altering the biophysical properties of mucin [ Sci Rep, 2024, 14(1):16568] | PubMed: 39019950 |
CFTR modulators response of S737F and T465N CFTR variants on patient-derived rectal organoids [ Orphanet J Rare Dis, 2024, 19(1):343] | PubMed: 39272186 |
CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants [ Pancreatology, 2024, S1424-3903(24)00066-8] | PubMed: 38493004 |
Functional rescue of CFTR in rectal organoids from patients carrying R334W variant by CFTR modulators and PDE4 inhibitor Roflumilast [ Respir Investig, 2024, 62(3):455-461] | PubMed: 38547757 |
Single-Stranded DNA with Internal Base Modifications Mediates Highly Efficient Gene Insertion in Primary Cells [ bioRxiv, 2024, 2024.02.01.578476] | PubMed: 38352420 |
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