Ivacaftor (VX-770) (VX-770) is a potentiator of CFTR targeting G551D-CFTR (EC50: 100 nM) and F508del-CFTR (EC50: 25 nM) in Fisher rat thyroid cells, respectively.

F508del CFTR:25 nM(EC50, Fisher rat thyroid cells), CFTR (G551D):100 nM(EC50, Fisher rat thyroid cells)

HEK293 cells were seeded on poly-lysine precoated six-well plates at a density of 1.3 x 10^6 cells/well. Six hours after seeding, cells were transiently transfected with 1μg of ABCB4-encoding plasmids using Turbofect, following the manufacturer's instructions. Twenty-four hours post-transfection, cells were washed twice with HBSS, then the medium was replaced by phenol red-free DMEM containing 0.5 mmol/L sodium taurocholate and 0.02% fatty acid–free bovine serum albumin (BSA) in the presence or absence of 10 μmol/L of ivacaftor, 50 μM/L of UDCA, and 10 μmol/L of ivacaftor plus 50 μM/L of UDCA. Media were collected after 24 hours [2].

Male mouse,Sprague?Dawley rats,beagle dog,and cynomolgus monkeys (n = 3/group) were administered a single iv dose of compound formulated in dimethyl isosorbide/ethanol/PEG400/5% dextrose in water (D5W) (10%/15%/35%/40%) at the nominal dose indicated in a dose volume of 1 mL/kg.Blood samples (0.3 mL,sodium heparin anticoagulant) were collected from an indwelling carotid cannula at the following nominal time points: at predose,5,15,30,and 45 min and 1,2,4,6,8,12,24,36,and 48 h following iv administration and at predose,0.25,0.50,1,1.5,2,4,8,12,and 24 h following oral administration.The concentration of compound in the plasma samples was determined with a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method,which had a lowest limit of quantitation (LLOQ) of 1 ng/mL and a linearity range between 1 and 2500 ng/mL [3].

依伐卡托, VX-770, Ivacaftor (VX-770)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 252 mg/mL (642.05 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 5 mg/mL (12.74 mM), Sonication is recommended.