Assay Detail
Binding
CHEMBL5731259
Review assay metadata, readout intent, target linkage, and publication context from the same page.
Aequorin Assay with Human NK-3 Receptor: Changes in intracellular calcium levels are a recognized indicator of G protein-coupled receptor activity. The efficacy of compounds of the invention to inhibit NKA-mediated NK-3 receptor activation was assessed by an in vitro Aequorin functional assay. Chinese Hamster Ovary recombinant cells expressing the human NK-3 receptor and a construct that encodes the photoprotein apoaequorin were used for this assay. In the presence of the cofactor coelenterazine, apoaequorin emits a measurable luminescence that is proportional to the amount of intracellular (cytoplasmic) free calcium.Antagonist TestingThe antagonist activity of compounds of the invention is measured following pre-incubation (3 minutes) of the compound (at various concentrations) with the cells, followed by addition of the reference agonist (NKA) at a final concentration equivalent to the EC80 (3 nM) and recording of emitted light (FDSS 6000 Hamamatsu) over the subsequent 90-second period. The intensity of the emitted light is integrated using the reader software. Compound antagonist activity is measured based on the concentration-dependent inhibition of the luminescence response to the addition of Neurokinin A.Inhibition curves are obtained for compounds of the invention and the concentrations of compounds which inhibit 50% of reference agonist response (IC50) were determined (see results in table 2 below). The IC50 values shown in table 2 indicate that compounds of the invention are potent NK-3 antagonist compounds.
141
Total Activities
47
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 |
Publication
Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
Activity Statistics
| Type | Count | Avg pChEMBL | Best pChEMBL |
|---|---|---|---|
| IC50 | 47 | 7.21 | 8.30 |
| kon | 47 | - | - |
| k_off | 47 | - | - |
Compounds Tested
| Compound | Name | Phase | Activities | Best pChEMBL |
|---|---|---|---|---|
| CHEMBL4108623 | — | — | 3 | 8.30 |
| CHEMBL3608688 | — | — | 3 | 8.15 |
| CHEMBL4113741 | — | — | 3 | 7.92 |
| CHEMBL4108583 | — | — | 3 | 7.80 |
| CHEMBL3608680 | FEZOLINETANT | 4.0 | 3 | 7.75 |
| CHEMBL4106866 | — | — | 3 | 7.72 |
| CHEMBL4112037 | — | — | 3 | 7.68 |
| CHEMBL4114280 | — | — | 3 | 7.52 |
| CHEMBL4115594 | — | — | 3 | 7.52 |
| CHEMBL3608687 | — | — | 3 | 7.50 |
| CHEMBL3964898 | — | — | 3 | 7.50 |
| CHEMBL4115295 | — | — | 3 | 7.48 |
| CHEMBL3936869 | — | — | 3 | 7.47 |
| CHEMBL4112806 | — | — | 3 | 7.41 |
| CHEMBL4110286 | — | — | 3 | 7.36 |
| CHEMBL3980803 | — | — | 3 | 7.36 |
| CHEMBL4112585 | — | — | 3 | 7.30 |
| CHEMBL4111714 | — | — | 3 | 7.30 |
| CHEMBL3899877 | — | — | 3 | 7.28 |
| CHEMBL3913001 | — | — | 3 | 7.27 |
| CHEMBL4113428 | — | — | 3 | 7.25 |
| CHEMBL3977343 | — | — | 3 | 7.24 |
| CHEMBL3927872 | — | — | 3 | 7.24 |
| CHEMBL3979723 | — | — | 3 | 7.21 |
| CHEMBL3891477 | — | — | 3 | 7.19 |
| CHEMBL4110770 | — | — | 3 | 7.15 |
| CHEMBL3608741 | — | — | 3 | 7.14 |
| CHEMBL4111859 | — | — | 3 | 7.13 |
| CHEMBL4110224 | — | — | 3 | 7.06 |
| CHEMBL3608740 | — | — | 3 | 7.03 |
Activity Data
| Compound | Name | Type | Rel. | Value | Units | pChEMBL |
|---|---|---|---|---|---|---|
| CHEMBL4108623 | — | IC50 | = | 5.0 | nM | 8.30 |
| CHEMBL3608688 | — | IC50 | = | 7.0 | nM | 8.15 |
| CHEMBL4113741 | — | IC50 | = | 12.0 | nM | 7.92 |
| CHEMBL4108583 | — | IC50 | = | 16.0 | nM | 7.80 |
| CHEMBL3608680 | FEZOLINETANT | IC50 | = | 18.0 | nM | 7.75 |
| CHEMBL4106866 | — | IC50 | = | 19.0 | nM | 7.72 |
| CHEMBL4112037 | — | IC50 | = | 21.0 | nM | 7.68 |
| CHEMBL4114280 | — | IC50 | = | 30.0 | nM | 7.52 |
| CHEMBL4115594 | — | IC50 | = | 30.0 | nM | 7.52 |
| CHEMBL3608687 | — | IC50 | = | 32.0 | nM | 7.50 |
| CHEMBL3964898 | — | IC50 | = | 32.0 | nM | 7.50 |
| CHEMBL4115295 | — | IC50 | = | 33.0 | nM | 7.48 |
| CHEMBL3936869 | — | IC50 | = | 34.0 | nM | 7.47 |
| CHEMBL4112806 | — | IC50 | = | 39.0 | nM | 7.41 |
| CHEMBL3980803 | — | IC50 | = | 44.0 | nM | 7.36 |
| CHEMBL4110286 | — | IC50 | = | 44.0 | nM | 7.36 |
| CHEMBL4112585 | — | IC50 | = | 50.0 | nM | 7.30 |
| CHEMBL4111714 | — | IC50 | = | 50.0 | nM | 7.30 |
| CHEMBL3899877 | — | IC50 | = | 52.0 | nM | 7.28 |
| CHEMBL3913001 | — | IC50 | = | 54.0 | nM | 7.27 |
| CHEMBL4113428 | — | IC50 | = | 56.0 | nM | 7.25 |
| CHEMBL3927872 | — | IC50 | = | 58.0 | nM | 7.24 |
| CHEMBL3977343 | — | IC50 | = | 57.0 | nM | 7.24 |
| CHEMBL3979723 | — | IC50 | = | 62.0 | nM | 7.21 |
| CHEMBL3891477 | — | IC50 | = | 64.0 | nM | 7.19 |
| CHEMBL4110770 | — | IC50 | = | 71.0 | nM | 7.15 |
| CHEMBL3608741 | — | IC50 | = | 73.0 | nM | 7.14 |
| CHEMBL4111859 | — | IC50 | = | 74.0 | nM | 7.13 |
| CHEMBL4110224 | — | IC50 | = | 87.0 | nM | 7.06 |
| CHEMBL3608740 | — | IC50 | = | 93.0 | nM | 7.03 |
| CHEMBL4115179 | — | IC50 | = | 110.0 | nM | 6.96 |
| CHEMBL4113908 | — | IC50 | = | 110.0 | nM | 6.96 |
| CHEMBL4110242 | — | IC50 | = | 120.0 | nM | 6.92 |
| CHEMBL3919172 | — | IC50 | = | 120.0 | nM | 6.92 |
| CHEMBL4112608 | — | IC50 | = | 130.0 | nM | 6.89 |
| CHEMBL3942295 | — | IC50 | = | 130.0 | nM | 6.89 |
| CHEMBL4112928 | — | IC50 | = | 136.0 | nM | 6.87 |
| CHEMBL5923889 | — | IC50 | = | 148.0 | nM | 6.83 |
| CHEMBL4109584 | — | IC50 | = | 150.0 | nM | 6.82 |
| CHEMBL3608682 | — | IC50 | = | 160.0 | nM | 6.80 |
| CHEMBL6036450 | — | IC50 | = | 170.0 | nM | 6.77 |
| CHEMBL3907155 | — | IC50 | = | 170.0 | nM | 6.77 |
| CHEMBL4113569 | — | IC50 | = | 204.0 | nM | 6.69 |
| CHEMBL4114258 | — | IC50 | = | 220.0 | nM | 6.66 |
| CHEMBL3895534 | — | IC50 | = | 220.0 | nM | 6.66 |
| CHEMBL4107267 | — | IC50 | = | 244.0 | nM | 6.61 |
| CHEMBL5898756 | — | IC50 | = | 285.0 | nM | 6.54 |
| CHEMBL4107267 | — | k_off | = | - | s-1 | - |
| CHEMBL3980803 | — | kon | = | - | — | - |
| CHEMBL4107267 | — | kon | = | - | — | - |