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Assay Detail

CHEMBL5731678

Review assay metadata, readout intent, target linkage, and publication context from the same page.

Binding
FRT Ion Flux Assay of F508del CFTR Potentiation: Fischer rat thyroid (FRT) cell lines stably expressing recombinant F508del V470 CFTR and halide-sensitive yellow fluorescent protein (Pedemonte et al., J. Clin. Invest. 115(9) 2564-71 (2005)) were seeded at 25,000 cells/well in 50 uL/well of culture medium into black-walled, clear bottom tissue-culture-treated 384-well plates (Corning, cat. no. 3712). After one day, the cells were pre-incubated at 27° C./5% CO2 for 16-24 hours. The cells were then washed with dPBS and treated with forskolin (20 uM) and test compound for 30 min by addition of 20 uL of compound dilution buffer (dPBS containing forskolin and test compound). Plates were loaded into FLIPR384 fluorescence imaging plate reader (Molecular Devices). After an initial fluorescence reading, iodide buffer (25 uL) (composition (in mM): 137 NaI, 1.5 K2PO4, 8.1 NaH2PO4, 2.7 KCl, 0.5 MgCl2, 1 CaCl2) was added and a second fluorescence reading was made after approximately 21 seconds. Data treatment involved division of the second fluorescence reading by the initial fluorescence reading, then scaling of the resulting normalized endpoint fluorescence with respect to the responses for DMSO (0%) and a positive control potentiator (100%).
159
Total Activities
34
Compounds Tested
3
Activity Types
0
Assay Parameters

Assay Information

Assay Type Binding
Confidence 8 — Homologous single protein target
Curated By Autocuration

Target

Cystic fibrosis transmembrane conductance regulator (CHEMBL4051)
Type SINGLE PROTEIN
Organism Homo sapiens

Publication

Bicyclic heteroaryl derivatives as CFTR potentiators
(2018)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
EC50 53 7.72 9.39
kon 53 - -
k_off 53 - -

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL5802461 3 9.39
CHEMBL5863288 6 9.25
CHEMBL5892004 6 9.25
CHEMBL6009312 3 9.24
CHEMBL6033456 6 9.21
CHEMBL6000653 9 8.73
CHEMBL5964878 6 8.67
CHEMBL5889215 6 8.51
CHEMBL5881985 3 8.50
CHEMBL5869365 6 8.47
CHEMBL5943989 6 8.38
CHEMBL5974038 3 8.33
CHEMBL5860580 6 8.32
CHEMBL5962153 6 8.30
CHEMBL5989702 6 8.13
CHEMBL5963315 6 8.06
CHEMBL5963506 6 8.04
CHEMBL5792842 6 7.97
CHEMBL5776338 3 7.85
CHEMBL5964959 3 7.76
CHEMBL6053005 6 7.75
CHEMBL5777022 3 7.74
CHEMBL5923614 3 7.63
CHEMBL6021895 3 7.58
CHEMBL6006507 6 7.53
CHEMBL5862902 3 7.52
CHEMBL5954441 6 7.50
CHEMBL5825851 3 7.43
CHEMBL5876993 3 7.38
CHEMBL5769135 6 7.30

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL5802461 EC50 = 0.41 nM 9.39
CHEMBL5863288 EC50 = 0.56 nM 9.25
CHEMBL5892004 EC50 = 0.56 nM 9.25
CHEMBL6009312 EC50 = 0.57 nM 9.24
CHEMBL6033456 EC50 = 0.62 nM 9.21
CHEMBL6000653 EC50 = 1.88 nM 8.73
CHEMBL5964878 EC50 = 2.13 nM 8.67
CHEMBL5889215 EC50 = 3.1 nM 8.51
CHEMBL5881985 EC50 = 3.13 nM 8.50
CHEMBL5869365 EC50 = 3.36 nM 8.47
CHEMBL5943989 EC50 = 4.17 nM 8.38
CHEMBL5974038 EC50 = 4.65 nM 8.33
CHEMBL5860580 EC50 = 4.76 nM 8.32
CHEMBL5962153 EC50 = 5.05 nM 8.30
CHEMBL6000653 EC50 = 5.83 nM 8.23
CHEMBL5863288 EC50 = 6.59 nM 8.18
CHEMBL5989702 EC50 = 7.4 nM 8.13
CHEMBL5963315 EC50 = 8.76 nM 8.06
CHEMBL5963506 EC50 = 9.14 nM 8.04
CHEMBL5792842 EC50 = 10.6 nM 7.97
CHEMBL6033456 EC50 = 12.5 nM 7.90
CHEMBL5892004 EC50 = 13.3 nM 7.88
CHEMBL5889215 EC50 = 13.8 nM 7.86
CHEMBL5776338 EC50 = 14.0 nM 7.85
CHEMBL5964959 EC50 = 17.2 nM 7.76
CHEMBL6053005 EC50 = 17.6 nM 7.75
CHEMBL5777022 EC50 = 18.4 nM 7.74
CHEMBL5923614 EC50 = 23.3 nM 7.63
CHEMBL6021895 EC50 = 26.0 nM 7.58
CHEMBL5792842 EC50 = 28.7 nM 7.54
CHEMBL6006507 EC50 = 29.6 nM 7.53
CHEMBL5862902 EC50 = 30.0 nM 7.52
CHEMBL5954441 EC50 = 31.8 nM 7.50
CHEMBL5964878 EC50 = 35.8 nM 7.45
CHEMBL5825851 EC50 = 37.2 nM 7.43
CHEMBL5876993 EC50 = 41.2 nM 7.38
CHEMBL5962153 EC50 = 45.2 nM 7.34
CHEMBL5963506 EC50 = 46.8 nM 7.33
CHEMBL6024579 EC50 = 50.3 nM 7.30
CHEMBL5769135 EC50 = 50.5 nM 7.30
CHEMBL5741266 EC50 = 54.4 nM 7.26
CHEMBL5989702 EC50 = 76.4 nM 7.12
CHEMBL5860580 EC50 = 78.8 nM 7.10
CHEMBL6000653 EC50 = 91.2 nM 7.04
CHEMBL5943989 EC50 = 95.9 nM 7.02
CHEMBL5954441 EC50 = 219.0 nM 6.66
CHEMBL5869365 EC50 = 249.0 nM 6.60
CHEMBL6053005 EC50 = 253.0 nM 6.60
CHEMBL5963315 EC50 = 266.0 nM 6.58
CHEMBL6062652 EC50 = 349.0 nM 6.46