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Assay Detail

CHEMBL5734029

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Binding
TGR5/CRE Luciferase Assay: In the following tables TGR5 activation by compounds and subsequent increase in intracellular cAMP were evaluated using a luciferase reporter gene assay. Human embryonic kidney (HEK) 293 cells were transiently co-transfected with pCMV tag4b-TGR5 h (to follow hTGR5 activation) or pCMV AC6-TGR5m (to follow mTGR5 activation) expression plasmids and the pCRE TA-Luciferase reporter plasmid using the JET PEI reagent (Polyplus transfection). Transfected cells were seeded in 96-well plates and incubated overnight with the test compounds at increasing concentrations tested in duplicate. Lithocolic acid (LCA) at 10 μM was used as a positive reference compound. The cAMP-dependent luciferase expression was followed using the BrightGlo reagent according to the manufacturer (Promega) instructions. Luminescence was read with a Mithras plate reader (Berthold). Data were expressed as percentage of the 10 μM LCA value and EC50 values were calculated using XL fit 5 software or GraphPad Prism 5. Concentration-response curves were fitted by a nonlinear regression analysis to a 4 parameter logistic equation.
72
Total Activities
23
Compounds Tested
3
Activity Types
0
Assay Parameters

Assay Information

Assay Type Binding
Organism Mus musculus
Confidence 9 — Direct single protein target
Curated By Autocuration

Target

G-protein coupled bile acid receptor 1 (CHEMBL1255150)
Type SINGLE PROTEIN
Organism Mus musculus

Publication

Imidazol- or 1,2,4-triazol-derivatives and their use
(2019)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
EC50 24 7.67 9.30
kon 24 - -
k_off 24 - -

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL4116055 3 9.30
CHEMBL4084668 3 9.00
CHEMBL4094487 3 9.00
CHEMBL4090147 3 8.70
CHEMBL4104359 6 8.40
CHEMBL4068227 3 8.32
CHEMBL4104779 3 8.30
CHEMBL4116110 3 8.15
CHEMBL4117224 3 8.00
CHEMBL4075688 3 7.92
CHEMBL5816372 3 7.75
CHEMBL6013098 3 7.58
CHEMBL5828397 3 7.54
CHEMBL4081298 3 7.36
CHEMBL4073081 3 7.36
CHEMBL5877867 3 7.17
CHEMBL4085664 3 7.17
CHEMBL4063932 3 7.05
CHEMBL4091702 3 6.85
CHEMBL4102610 3 6.75
CHEMBL4060122 3 6.43
CHEMBL4088938 3 6.29
CHEMBL4085777 3 6.03

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL4116055 EC50 = 0.5 nM 9.30
CHEMBL4094487 EC50 = 1.0 nM 9.00
CHEMBL4084668 EC50 = 1.0 nM 9.00
CHEMBL4090147 EC50 = 2.0 nM 8.70
CHEMBL4104359 EC50 = 4.0 nM 8.40
CHEMBL4068227 EC50 = 4.8 nM 8.32
CHEMBL4104779 EC50 = 5.0 nM 8.30
CHEMBL4116110 EC50 = 7.0 nM 8.15
CHEMBL4117224 EC50 = 10.0 nM 8.00
CHEMBL4075688 EC50 = 12.0 nM 7.92
CHEMBL4104359 EC50 = 17.0 nM 7.77
CHEMBL5816372 EC50 = 18.0 nM 7.75
CHEMBL6013098 EC50 = 26.0 nM 7.58
CHEMBL5828397 EC50 = 29.0 nM 7.54
CHEMBL4073081 EC50 = 44.0 nM 7.36
CHEMBL4081298 EC50 = 44.0 nM 7.36
CHEMBL4085664 EC50 = 68.0 nM 7.17
CHEMBL5877867 EC50 = 68.0 nM 7.17
CHEMBL4063932 EC50 = 90.0 nM 7.05
CHEMBL4091702 EC50 = 140.0 nM 6.85
CHEMBL4102610 EC50 = 180.0 nM 6.75
CHEMBL4060122 EC50 = 370.0 nM 6.43
CHEMBL4088938 EC50 = 510.0 nM 6.29
CHEMBL4085777 EC50 = 940.0 nM 6.03
CHEMBL5877867 k_off = - s-1 -
CHEMBL4090147 k_off = - s-1 -
CHEMBL5877867 kon = - -
CHEMBL5828397 kon = - -
CHEMBL5828397 k_off = - s-1 -
CHEMBL6013098 k_off = - s-1 -
CHEMBL4104359 kon = - -
CHEMBL4085664 kon = - -
CHEMBL4085664 k_off = - s-1 -
CHEMBL4081298 kon = - -
CHEMBL4081298 k_off = - s-1 -
CHEMBL4075688 kon = - -
CHEMBL4075688 k_off = - s-1 -
CHEMBL4090147 kon = - -
CHEMBL4117224 kon = - -
CHEMBL4094487 k_off = - s-1 -
CHEMBL4094487 kon = - -
CHEMBL6013098 kon = - -
CHEMBL4116055 kon = - -
CHEMBL4068227 k_off = - s-1 -
CHEMBL4068227 kon = - -
CHEMBL4116055 k_off = - s-1 -
CHEMBL4088938 k_off = - s-1 -
CHEMBL4088938 kon = - -
CHEMBL4091702 k_off = - s-1 -
CHEMBL4117224 k_off = - s-1 -