Lumacaftor, Inhibitor

Lumacaftor(VX 809)

Cat. Num. AAA575979

• Purity: 99.72%
• Synonyms: Lumacaftor; Lumacaftor(VX 809); inhibitor

• Purity/Purification: 99.72%
• Form/Format: Solid

• Molecular Formula: C24H18F2N2O5
• Targets(IC50): F508del-CFTR: 0.1uM(EC50)
• In vitro: In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, Lumacaftor (VX-809) improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50: 81 nM), a level associated with mild CF in patients with less disruptive CFTR mutations [1]. VX-809 produced a concentration-dependent increase in the HRP luminescence signal after incubation with cells at 37°C or 27°C in both cell lines, with a similar EC50 value of approximately 0.3 uM [2].
• In vivo: Oral dosing of 1 mg/kg VX-809 in male Sprague-Dawley rats results in a Cmax of 2.4+1.3 uM with a t1/2 of 7.7+0.4 h (mean±SD; n=3), indicating that that VX-809 is orally bioavailable and able to reach plasma levels that significantly exceeded EC50s for F508del-CFTR correction[1].
• Kinase Assay: In one set of assays, R1070W-ΔF508-CFTR-HRP (R1070W-HRP)–expressing CFBE41o- cells were incubated with 100 ul medium containing 25 uM test compounds and 0.5 ug/ml doxycycline for 24 hours at 37°C. In a second set of assays, ΔF508-CFTR-HRP (ΔF508-HRP)–expressing CFBE41o- cells were incubated with 100 ul medium containing 25 uM test compounds, 2 uM VX-809, and 0.5 ug/ml doxycycline for 24 hours at 37°C. All compound plates contained negative controls (DMSO vehicle) and positive controls [2 uM VX-809]. In both assays, the cells were washed four times with PBS, and HRP activity was assayed by the addition of 50 ul/well of HRP substrate. After shaking for 5 minutes, chemiluminescence was measured using a Tecan Infinite M1000 plate reader (Tecan Groups Ltd, Mannedorf, Switzerland) equipped with an automated stacker (integration time, 100 milliseconds). Z' is defined as = 1 - [(3 × standard deviation of maximum signal control + 3 × standard deviation of minimum signal control)/absolute (mean of maximum signal control mean of minimum signal control)] [2].
• Preparation and Storage: 0-4°C for short term (days to weeks), or -20°C for long term (months).

Structure

Related Product Information for Lumacaftor, inhibitor

VX-809 is a CFTR modulator that corrects the folding and trafficking of CFTR protein. It enhances F508del-CFTR protein maturation in FRT cells (EC50: 100 nM).