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Assay Detail

CHEMBL5731052

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

Binding
Fatty Acid Synthase Keto-reductase Domain (FASN KR) Inhibition: 10 μL assay buffer (100 mM KH2PO4 pH 7.5) was added to a 384-well clear plate (costar 3702). 0.3 μL compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO, 10 μL hFASN enzyme (full length, 300 ng, purified in house) and 360 μM NADPH (except in blank) were then added. Then, 10 μL 180 mM ethyl acetoacetate (Aldrich 688983) was added, mixed and immediately thereafter, the absorbance at 340 nm (T1) by Multiscan (Labsystems) was measured. After 20 minutes incubation at room temperature the plate was measured again (T2).Enzymatic activity of FASN KR was measured as the oxidation of NADPH to NADP+ (a decrease in NADPH signal was observed at OD 340 nm). The decrease in absorbance was calculated as (Absorbance before incubation T1)−(Absorbance following incubation T2).Raw data generated by the instrument were normalized to % Controlmin values, which were calculated as: % Controlmin=100*(x−mLC)/(mHC−mLC)where mLC and mHC were the means of the low control wells and high control wells on the plate, after manual exclusion of outliers. A plot of Controlmin versus test compound concentration was fitted to a 4-parameter logistic curve using a non-linear least squares regression method. From the plot, an IC50 (concentration at which 50% inhibition is achieved) was calculated. pIC50 values were calculated as −log(IC50), when IC50 is expressed in molar units.
210
Total Activities
69
Compounds Tested
3
Activity Types
0
Assay Parameters

Assay Information

Assay Type Binding
Confidence 0 — Uncurated / Unknown
Curated By Autocuration

Target

Unchecked (CHEMBL612545)
Type UNCHECKED

Publication

Imidazolin-5-one derivative useful as FASN inhibitors for the treatment of cancer
(2017)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
IC50 70 6.55 7.60
kon 70 - -
k_off 70 - -

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL6034162 3 7.60
CHEMBL5876718 3 7.38
CHEMBL5969695 3 7.32
CHEMBL5922011 3 7.30
CHEMBL5957211 3 7.28
CHEMBL5839177 3 7.27
CHEMBL5760930 3 7.27
CHEMBL3617742 3 7.25
CHEMBL5788711 3 7.23
CHEMBL5977971 3 7.20
CHEMBL5863279 3 7.17
CHEMBL5855781 3 7.17
CHEMBL5858978 3 7.14
CHEMBL5974575 3 7.13
CHEMBL5750822 3 7.06
CHEMBL6035580 3 6.97
CHEMBL6030711 3 6.96
CHEMBL5943600 3 6.95
CHEMBL5824348 3 6.92
CHEMBL6032013 3 6.90
CHEMBL6051120 3 6.89
CHEMBL3617741 3 6.86
CHEMBL5802991 3 6.81
CHEMBL5990353 3 6.80
CHEMBL5788930 3 6.76
CHEMBL5985038 3 6.75
CHEMBL6039031 3 6.73
CHEMBL5917086 6 6.67
CHEMBL5938748 3 6.65
CHEMBL5892433 3 6.62

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL6034162 IC50 = 25.1 nM 7.60
CHEMBL5876718 IC50 = 41.7 nM 7.38
CHEMBL5969695 IC50 = 47.9 nM 7.32
CHEMBL5922011 IC50 = 50.1 nM 7.30
CHEMBL5957211 IC50 = 52.5 nM 7.28
CHEMBL5760930 IC50 = 53.7 nM 7.27
CHEMBL5839177 IC50 = 53.7 nM 7.27
CHEMBL3617742 IC50 = 56.2 nM 7.25
CHEMBL5788711 IC50 = 58.9 nM 7.23
CHEMBL5977971 IC50 = 63.1 nM 7.20
CHEMBL5855781 IC50 = 67.6 nM 7.17
CHEMBL5863279 IC50 = 67.6 nM 7.17
CHEMBL5858978 IC50 = 72.4 nM 7.14
CHEMBL5974575 IC50 = 74.1 nM 7.13
CHEMBL5750822 IC50 = 87.1 nM 7.06
CHEMBL6035580 IC50 = 107.0 nM 6.97
CHEMBL6030711 IC50 = 110.0 nM 6.96
CHEMBL5943600 IC50 = 112.0 nM 6.95
CHEMBL5824348 IC50 = 120.0 nM 6.92
CHEMBL6032013 IC50 = 126.0 nM 6.90
CHEMBL6051120 IC50 = 129.0 nM 6.89
CHEMBL3617741 IC50 = 138.0 nM 6.86
CHEMBL5802991 IC50 = 155.0 nM 6.81
CHEMBL5990353 IC50 = 158.0 nM 6.80
CHEMBL5788930 IC50 = 174.0 nM 6.76
CHEMBL5985038 IC50 = 178.0 nM 6.75
CHEMBL6039031 IC50 = 186.0 nM 6.73
CHEMBL5917086 IC50 = 214.0 nM 6.67
CHEMBL5938748 IC50 = 224.0 nM 6.65
CHEMBL5892433 IC50 = 240.0 nM 6.62
CHEMBL6003285 IC50 = 251.0 nM 6.60
CHEMBL5917748 IC50 = 269.0 nM 6.57
CHEMBL5822742 IC50 = 282.0 nM 6.55
CHEMBL5767579 IC50 = 302.0 nM 6.52
CHEMBL3617744 IC50 = 324.0 nM 6.49
CHEMBL3617743 IC50 = 347.0 nM 6.46
CHEMBL5749645 IC50 = 355.0 nM 6.45
CHEMBL5865379 IC50 = 355.0 nM 6.45
CHEMBL5963009 IC50 = 363.0 nM 6.44
CHEMBL5896696 IC50 = 389.0 nM 6.41
CHEMBL5929792 IC50 = 389.0 nM 6.41
CHEMBL4127768 IC50 = 417.0 nM 6.38
CHEMBL5759977 IC50 = 417.0 nM 6.38
CHEMBL5777034 IC50 = 437.0 nM 6.36
CHEMBL5811059 IC50 = 468.0 nM 6.33
CHEMBL5881362 IC50 = 468.0 nM 6.33
CHEMBL5976657 IC50 = 468.0 nM 6.33
CHEMBL5791788 IC50 = 479.0 nM 6.32
CHEMBL5918198 IC50 = 537.0 nM 6.27
CHEMBL6006978 IC50 = 550.0 nM 6.26