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Assay Detail

CHEMBL5731677

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Binding
Chamber Electrophysiology Assay of CFTR Potentiation in CF Bronchial Epithelial Cells: Primary cystic fibrosis human bronchial epithelial (CF hBE) cells were expanded and cultured according to published methods (Neuberger et al., Ch. 4 of Cystic Fibrosis, Methods in Molecular Biology vol. 741, pp. 39-54 (2011)). Well-differentiated cells (>30 days at air/liquid interface) on Snapwell filters (Corning Costar, cat. no. 3801) were mounted in Ussing chambers (Physiologic Instruments, Inc., San Diego, Calif.). F508del/F508del cultures were assayed at 27° C. and G551D/F508del cells were assayed at 35° C. HEPES buffered physiological saline (composition (in mM): 137 NaCl, 4 KCl, 1 MgCl2, 1.8 CaCl2, 10 HEPES Na) was used in both apical and basolateral chambers. Chambers were bubbled with air to promote mixing and the voltage was clamped to zero. Amiloride (30 uM), forskolin (10 uM), test compound (4 increasing concentrations), and CFTRinh-172 (20 uM) were added sequentially with 20-25 minutes between additions. Short-circuit currents were acquired and analyzed using LabScribe2. Test compound responses were scaled relative to responses for DMSO (0%) and the maximal response of a positive control potentiator (100%).
165
Total Activities
36
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 55 7.95 9.70
kon 55 - -
k_off 55 - -

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL5863288 6 9.70
CHEMBL5861582 3 9.40
CHEMBL5892004 6 9.38
CHEMBL6033456 6 9.38
CHEMBL5881985 3 9.18
CHEMBL6009312 3 9.07
CHEMBL5802461 3 8.98
CHEMBL5860580 6 8.81
CHEMBL5889215 6 8.78
CHEMBL6000653 9 8.70
CHEMBL5869365 6 8.70
CHEMBL5964878 9 8.52
CHEMBL5811687 3 8.41
CHEMBL5974038 3 8.40
CHEMBL5962153 6 8.26
CHEMBL5989702 6 8.19
CHEMBL5943989 6 8.16
CHEMBL5963315 6 8.13
CHEMBL5862902 3 8.05
CHEMBL6053005 6 8.00
CHEMBL5776338 3 7.98
CHEMBL5963506 6 7.95
CHEMBL5964959 3 7.89
CHEMBL5792842 6 7.84
CHEMBL5777022 3 7.80
CHEMBL6006507 6 7.71
CHEMBL6021895 3 7.70
CHEMBL5923614 3 7.57
CHEMBL5876993 3 7.55
CHEMBL5825851 3 7.54

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL5863288 EC50 = 0.2 nM 9.70
CHEMBL5861582 EC50 = 0.4 nM 9.40
CHEMBL6033456 EC50 = 0.42 nM 9.38
CHEMBL5892004 EC50 = 0.42 nM 9.38
CHEMBL5881985 EC50 = 0.66 nM 9.18
CHEMBL6009312 EC50 = 0.86 nM 9.07
CHEMBL5802461 EC50 = 1.05 nM 8.98
CHEMBL5860580 EC50 = 1.53 nM 8.81
CHEMBL5889215 EC50 = 1.67 nM 8.78
CHEMBL5869365 EC50 = 2.0 nM 8.70
CHEMBL6000653 EC50 = 2.0 nM 8.70
CHEMBL5863288 EC50 = 2.0 nM 8.70
CHEMBL5892004 EC50 = 3.0 nM 8.52
CHEMBL5964878 EC50 = 3.02 nM 8.52
CHEMBL5811687 EC50 = 3.87 nM 8.41
CHEMBL5974038 EC50 = 4.0 nM 8.40
CHEMBL6033456 EC50 = 4.0 nM 8.40
CHEMBL6000653 EC50 = 4.93 nM 8.31
CHEMBL5889215 EC50 = 5.0 nM 8.30
CHEMBL5962153 EC50 = 5.48 nM 8.26
CHEMBL5989702 EC50 = 6.48 nM 8.19
CHEMBL5943989 EC50 = 6.96 nM 8.16
CHEMBL5963315 EC50 = 7.48 nM 8.13
CHEMBL5964878 EC50 = 7.86 nM 8.11
CHEMBL5862902 EC50 = 8.94 nM 8.05
CHEMBL6053005 EC50 = 9.95 nM 8.00
CHEMBL5776338 EC50 = 10.4 nM 7.98
CHEMBL5963506 EC50 = 11.2 nM 7.95
CHEMBL5964959 EC50 = 13.0 nM 7.89
CHEMBL5792842 EC50 = 14.6 nM 7.84
CHEMBL5777022 EC50 = 16.0 nM 7.80
CHEMBL6006507 EC50 = 19.3 nM 7.71
CHEMBL6021895 EC50 = 19.8 nM 7.70
CHEMBL5964878 EC50 = 20.5 nM 7.69
CHEMBL5792842 EC50 = 20.9 nM 7.68
CHEMBL5923614 EC50 = 27.1 nM 7.57
CHEMBL5876993 EC50 = 28.4 nM 7.55
CHEMBL5825851 EC50 = 29.2 nM 7.54
CHEMBL5860580 EC50 = 31.0 nM 7.51
CHEMBL5954441 EC50 = 31.5 nM 7.50
CHEMBL5962153 EC50 = 33.5 nM 7.47
CHEMBL6000653 EC50 = 36.6 nM 7.44
CHEMBL5943989 EC50 = 48.0 nM 7.32
CHEMBL5963506 EC50 = 51.1 nM 7.29
CHEMBL6024579 EC50 = 74.4 nM 7.13
CHEMBL6053005 EC50 = 73.7 nM 7.13
CHEMBL5869365 EC50 = 115.0 nM 6.94
CHEMBL5741266 EC50 = 116.0 nM 6.94
CHEMBL5961016 EC50 = 123.0 nM 6.91
CHEMBL5769135 EC50 = 147.0 nM 6.83