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Assay Detail

CHEMBL3707930

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Binding
Time Resolved Fluorescence Energy Transfer (TR-FRET) Assay: The inhibition of p53-Hdm2 and p53-Hdm4 interactions is measured by time resolved fluorescence energy transfer (TR-FRET). Fluorescence energy transfer (or Foerster resonance energy transfer) describes an energy transfer between donor and acceptor fluorescent molecules. For this assay, MDM2 protein (amino acids 2-188) and MDM4 protein (amino acids 2-185), tagged with a C-terminal Biotin moiety, are used in combination with a Europium labeled streptavidin (Perkin Elmer, Inc., Waltham, Mass., USA) serving as the donor fluorophore. The p53 derived, Cy5 labeled peptide Cy5-TFSDLWKLL (p53 aa 18-26) is the energy acceptor. Upon excitation of the donor molecule at 340 nm, binding interaction between MDM2 or MDM4 and the p53 peptide induces energy transfer and enhanced response at the acceptor emission wavelength at 665 nm. Disruption of the formation of the p53-MDM2 or p53-MDM4 complex due to an inhibitor molecule binding to the p53 binding site of MDM2 or MDM4 results in increased donor emission.
75
Total Activities
74
Compounds Tested
1
Activity Types
0
Assay Parameters

Assay Information

Assay Type Binding
Organism Homo sapiens
Confidence 9 — Direct single protein target
Curated By Autocuration

Target

Protein Mdm4 (CHEMBL1255126)
Type SINGLE PROTEIN
Organism Homo sapiens

Publication

Substituted isoquinolinones and quinazolinones
(2015)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
IC50 75 4.89 5.87

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL3683182 1 5.87
CHEMBL3683183 1 5.81
CHEMBL3601401 1 5.79
CHEMBL3601397 1 5.78
CHEMBL3683171 1 5.77
CHEMBL3683173 1 5.76
CHEMBL3683163 1 5.74
CHEMBL3683172 1 5.69
CHEMBL3601398 CGM-097 1.0 1 5.68
CHEMBL3683178 1 5.67
CHEMBL3601323 1 5.65
CHEMBL3683160 1 5.64
CHEMBL3683139 1 5.64
CHEMBL3683159 1 5.55
CHEMBL3601322 2 5.54
CHEMBL3683156 1 5.54
CHEMBL3683162 1 5.52
CHEMBL3601403 1 5.43
CHEMBL3601319 1 5.39
CHEMBL3601320 1 5.39
CHEMBL3683179 1 5.38
CHEMBL3683138 1 5.34
CHEMBL3683177 1 5.29
CHEMBL3683133 1 5.22
CHEMBL3914742 1 5.17
CHEMBL3683161 1 5.15
CHEMBL3683135 1 5.10
CHEMBL3601402 1 5.09
CHEMBL3683124 1 5.09
CHEMBL3683174 1 5.08

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL3683182 IC50 = 1360.0 nM 5.87
CHEMBL3683183 IC50 = 1560.0 nM 5.81
CHEMBL3601401 IC50 = 1630.0 nM 5.79
CHEMBL3601397 IC50 = 1660.0 nM 5.78
CHEMBL3683171 IC50 = 1700.0 nM 5.77
CHEMBL3683173 IC50 = 1730.0 nM 5.76
CHEMBL3683163 IC50 = 1840.0 nM 5.74
CHEMBL3683172 IC50 = 2030.0 nM 5.69
CHEMBL3601398 CGM-097 IC50 = 2100.0 nM 5.68
CHEMBL3683178 IC50 = 2150.0 nM 5.67
CHEMBL3601323 IC50 = 2240.0 nM 5.65
CHEMBL3683160 IC50 = 2310.0 nM 5.64
CHEMBL3683139 IC50 = 2300.0 nM 5.64
CHEMBL3683159 IC50 = 2800.0 nM 5.55
CHEMBL3683156 IC50 = 2890.0 nM 5.54
CHEMBL3601322 IC50 = 2880.0 nM 5.54
CHEMBL3683162 IC50 = 3010.0 nM 5.52
CHEMBL3601403 IC50 = 3750.0 nM 5.43
CHEMBL3601319 IC50 = 4060.0 nM 5.39
CHEMBL3601320 IC50 = 4040.0 nM 5.39
CHEMBL3683179 IC50 = 4130.0 nM 5.38
CHEMBL3683138 IC50 = 4540.0 nM 5.34
CHEMBL3683177 IC50 = 5090.0 nM 5.29
CHEMBL3683133 IC50 = 6010.0 nM 5.22
CHEMBL3914742 IC50 = 6830.0 nM 5.17
CHEMBL3683161 IC50 = 7050.0 nM 5.15
CHEMBL3683135 IC50 = 8010.0 nM 5.10
CHEMBL3601402 IC50 = 8120.0 nM 5.09
CHEMBL3683124 IC50 = 8130.0 nM 5.09
CHEMBL3683174 IC50 = 8340.0 nM 5.08
CHEMBL3683180 IC50 = 8580.0 nM 5.07
CHEMBL3683166 IC50 = 9000.0 nM 5.05
CHEMBL3683157 IC50 = 9870.0 nM 5.01
CHEMBL3683134 IC50 = 10400.0 nM 4.98
CHEMBL3683154 IC50 = 11210.0 nM 4.95
CHEMBL3683123 IC50 = 11380.0 nM 4.94
CHEMBL3683169 IC50 = 12500.0 nM 4.90
CHEMBL3683151 IC50 = 16720.0 nM 4.78
CHEMBL3683128 IC50 = 17460.0 nM 4.76
CHEMBL3683155 IC50 = 17860.0 nM 4.75
CHEMBL3683152 IC50 = 18150.0 nM 4.74
CHEMBL3601316 IC50 = 19320.0 nM 4.71
CHEMBL3683158 IC50 = 22750.0 nM 4.64
CHEMBL3683122 IC50 = 23720.0 nM 4.62
CHEMBL3683137 IC50 = 24510.0 nM 4.61
CHEMBL3683165 IC50 = 24890.0 nM 4.60
CHEMBL3683141 IC50 = 26740.0 nM 4.57
CHEMBL3683164 IC50 = 27900.0 nM 4.55
CHEMBL3683143 IC50 = 29060.0 nM 4.54
CHEMBL3683144 IC50 = 30110.0 nM 4.52