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Assay Detail

CHEMBL3706083

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

Binding
Homogeneous Time-Resolved FRET Assay: The protocol that was used to determine the recited values isdescribed as follows.BACE1 HTRF FRET AssayReagentsNa+-Acetate pH 5.01% Brij-35GlycerolDimethyl Sulfoxide (DMSO)Recombinant human soluble BACE1 catalytic domain (>95% pure)APP Swedish mutant peptide substrate (QSY7-APPswe-Eu):QSY7-EISEVNLDAEFC-Europium-amideA homogeneous time-resolved FRET assay was used to determine IC50 values for inhibitors of the soluble human BACE1 catalytic domain. This assay monitored the increase of 620 nm fluorescence that resulted from BACE1 cleavage of an APPswedish APPswe mutant peptide FRET substrate (QSY7-EISEVNLDAEFC-Europium-amide). This substrate contained an N-terminal QSY7 moiety that served as a quencher of the C-terminal Europium fluorophore (620 nm Em). In the absence of enzyme activity, 620 nm fluorescence was low in the assay and increased linearly over 3 hours in the presence of uninhibited BACE1 enzyme.
11
Total Activities
11
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

Beta-secretase 1 (CHEMBL4822)
Type SINGLE PROTEIN
Organism Homo sapiens

Publication

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use
(2015)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
Ki 11 8.44 9.02

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL3672916 1 9.02
CHEMBL3672919 1 8.98
CHEMBL3672917 1 8.90
CHEMBL3672923 1 8.79
CHEMBL3301601 VERUBECESTAT 3.0 1 8.76
CHEMBL3259832 1 8.62
CHEMBL3672920 1 8.52
CHEMBL3702860 1 8.31
CHEMBL3672918 1 8.00
CHEMBL3672921 1 7.59
CHEMBL3672922 1 7.34

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL3672916 Ki = 0.949 nM 9.02
CHEMBL3672919 Ki = 1.05 nM 8.98
CHEMBL3672917 Ki = 1.261 nM 8.90
CHEMBL3672923 Ki = 1.64 nM 8.79
CHEMBL3301601 VERUBECESTAT Ki = 1.753 nM 8.76
CHEMBL3259832 Ki = 2.387 nM 8.62
CHEMBL3672920 Ki = 3.0 nM 8.52
CHEMBL3702860 Ki = 4.88 nM 8.31
CHEMBL3672918 Ki = 10.0 nM 8.00
CHEMBL3672921 Ki = 25.6 nM 7.59
CHEMBL3672922 Ki = 46.0 nM 7.34