包装 | 价格(元) |
10mM (in 1mL DMSO) | 电议 |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
Inhibitory activities | Lumacaftor(VX-809), succeeded in a Phase III clinical trial, is a cystic fibrosis transmembrane conductance regulator (CFTR) corrector. VX-809 had been shown to increase membrane expression of mutant channels and cell surface density of functional F508del-CFTR in vitro. |
Cell | Human bronchial epithelial (HBE) cells, F508del-CFBE cells, CF-HBE cells (F508del/F508del) and A549 cells. |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | Expose time: 48 h. |
Applications | In human bronchial epithelial (HBE) cells, VX-809 could increase F508del-CFTR Cl secretion, and increase FEV1 by an average of 3-5% in CF patients with homozygous for the F508del-CFTR mutation in combination with VX-770. |
Patients model | Patients with Cystic Fibrosis Homozygous |
Dosage form | 600 mg once daily or 400 mg every 12 hours |
Preparation method | orally administered |
Applications | At the plasma membrane, it increased F508del-CFTR levels. Alone or in combination with ivacaftor improved clinical outcome in patients with homozygous for the F508del mutation, Lumacaftor acted an key role in the treatment of biochemical abnormalities in CF. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. The actual solubility may slightly differ with the theoretical value. |
产品描述 | VX-809 is a CFTR corrector that partially restores the function of F508del-CFTR. In Fischer rat thyroid (FRT) cells, it increases F508del-CFTR maturation at EC50 of 0.1 μM, and elevates F508del-CFTR–mediated chloride transport at EC50 of 0.5 μM [1]. It has no effect of other ion channels (hERG), transporter (P-gp) and disease-causing mislocalized proteins (α1-antitrypsin Z mutant) [1]. VX-809 stabilizes N-terminal fragment of CFTR that contain MSD1 by altering its protein conformation [2, 3]. Homozygous F508del-CFTR is the most common mutation in cystic fibrosis (CF) patients, accounting for 66–70% of CF cases worldwide. In cultured human bronchial epithelial cells that are homozygous for F508del, VX-809 restored the CFTR function and improved chloride and fluid Transport [1]. The combination of CFTR potentiators and VX-809 further improved the function of F508del-CFTR [4]. VX-809 has been tested in several clinical trials. Although it had minimal benefit to F508del-CFTR homozygous patients as a monotherapy [4], the result of Phase 2 study of VX-809 and KALYDECO combination showed significant improvements in lung function in CF patients with homozygous F508del-CFTR [5]. VX-809 is currently under investigation in two phase 3 trials. References: |