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Assay Detail

CHEMBL5732791

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Binding
Inhibition Assay: Key enzyme kinetic parameters for one class I HDAC (HDAC8) and one class Ha HDAC (HDAC4) were determined using commercially available human recombinant HDAC enzymes (BPS Bioscience, San Diego, Calif.) and fluorogenic HDAC assay kits (BPS Bioscience). Kinetic parameters were determined by performing HDAC activity assays at varied concentrations of the HDAC substrate according to the manufacturer's protocol. Assay data were analyzed via non-linear regression (GraphPad Software, Inc., CA). Inhibition assays were used to determine the half maximal inhibitory concentration, IC50, for tropolone analogs in HDAC8 and HDAC6. The potent hydroxamic acid HDAC inhibitor, Trichostatin A (TSA), provided in the assay kit, served as a control for the assays. IC50 values for the tropolone analogs were converted to inhibition constants, Ki, for each of the inhibitors using the KM value in accordance with the techniques previously described by Cheng and Prusoff.
36
Total Activities
12
Compounds Tested
3
Activity Types
0
Assay Parameters

Assay Information

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

Target

Histone deacetylase 8 (CHEMBL3192)
Type SINGLE PROTEIN
Organism Homo sapiens

Publication

Substituted tropolone derivatives and methods of use
(2017)

Activity Statistics

Type Count Avg pChEMBL Best pChEMBL
Ki 12 8.68 10.40
kon 12 - -
k_off 12 - -

Compounds Tested

Compound Name Phase Activities Best pChEMBL
CHEMBL2408241 3 10.40
CHEMBL2408239 3 9.85
CHEMBL2408237 3 9.77
CHEMBL2408240 3 9.36
CHEMBL5802986 3 8.87
CHEMBL2408244 3 8.85
CHEMBL2408245 3 8.57
CHEMBL2408238 3 8.12
CHEMBL2408246 3 8.00
CHEMBL2408242 3 7.71
CHEMBL2408247 3 7.63
CHEMBL48310 HINOKITIOL 3 6.98

Activity Data

Compound Name Type Rel. Value Units pChEMBL
CHEMBL2408241 Ki = 0.04 nM 10.40
CHEMBL2408239 Ki = 0.14 nM 9.85
CHEMBL2408237 Ki = 0.17 nM 9.77
CHEMBL2408240 Ki = 0.44 nM 9.36
CHEMBL5802986 Ki = 1.36 nM 8.87
CHEMBL2408244 Ki = 1.42 nM 8.85
CHEMBL2408245 Ki = 2.69 nM 8.57
CHEMBL2408238 Ki = 7.63 nM 8.12
CHEMBL2408246 Ki = 10.1 nM 8.00
CHEMBL2408242 Ki = 19.4 nM 7.71
CHEMBL2408247 Ki = 23.3 nM 7.63
CHEMBL48310 HINOKITIOL Ki = 105.0 nM 6.98
CHEMBL2408242 k_off = - s-1 -
CHEMBL2408242 kon = - -
CHEMBL2408241 k_off = - s-1 -
CHEMBL2408241 kon = - -
CHEMBL2408240 k_off = - s-1 -
CHEMBL2408240 kon = - -
CHEMBL2408239 k_off = - s-1 -
CHEMBL2408239 kon = - -
CHEMBL2408238 k_off = - s-1 -
CHEMBL2408238 kon = - -
CHEMBL2408237 k_off = - s-1 -
CHEMBL2408237 kon = - -
CHEMBL5802986 kon = - -
CHEMBL5802986 k_off = - s-1 -
CHEMBL2408247 k_off = - s-1 -
CHEMBL2408244 kon = - -
CHEMBL2408244 k_off = - s-1 -
CHEMBL2408247 kon = - -
CHEMBL48310 HINOKITIOL kon = - -
CHEMBL48310 HINOKITIOL k_off = - s-1 -
CHEMBL2408245 kon = - -
CHEMBL2408245 k_off = - s-1 -
CHEMBL2408246 kon = - -
CHEMBL2408246 k_off = - s-1 -