Thyroid receptor (TR) regulates many homeostatic processes including basal metabolism, cardiovascular function, body weight, and lipid trafficking. TR modulators are potential therapeutics for obesity and hyperlipidemias but current thyroid analogs have undesirable side effects, particularly cardiac stimulation. This secondary assay characterized compounds identified in the qHTS for Inhibitors of more ..
Target
Tested Compounds:
Depositor Specified Assays
| AID | Name | Type | Probe | Comment |
|---|---|---|---|---|
| 1469 | qHTS for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 | confirmatory | ||
| 1479 | Total Fluorescence Counterscreen for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 | confirmatory | ||
| 1570 | Concentration Response Confirmation Assay for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2, Fluorescein Fluoroprobe | confirmatory | ||
| 1571 | Total Fluorescence Confirmation Counterscreen for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2, Fluorescein Fluoroprobe | confirmatory | ||
| 1572 | Total Fluorescence Confirmation Counterscreen for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 | confirmatory | ||
| 1573 | Concentration Response Confirmation Assay for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 | confirmatory | ||
| 1485 | Quantitative High-Throughput Screen for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2: Summary | summary | ||
| 2512 | qHTS Assay for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2: Probe Summary | summary | 1 |
Description:
NIH Molecular Libraries Probe Production Network [MLPCN]
NIH Chemical Genomics Center [NCGC]
MLPCN Grant: DK058080
Assay Provider: R. Kip Guy, St. Jude Children's Research Hospital
NCGC Assay Overview:
Thyroid receptor (TR) regulates many homeostatic processes including basal metabolism, cardiovascular function, body weight, and lipid trafficking. TR modulators are potential therapeutics for obesity and hyperlipidemias but current thyroid analogs have undesirable side effects, particularly cardiac stimulation. This secondary assay characterized compounds identified in the qHTS for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 (PubChem AID 1485) for selectivity against the androgen receptor (AR). This assay detects interaction of the ligand-binding domain of human AR with a Texas Red labeled SRC2-3 peptide, corresponding to a 20 amino acid region of the nuclear receptor interaction domain. Small molecule inhibitors that block the interaction of AR and SRC2-3 are detected by a decrease in fluorescence polarization.
NIH Chemical Genomics Center [NCGC]
MLPCN Grant: DK058080
Assay Provider: R. Kip Guy, St. Jude Children's Research Hospital
NCGC Assay Overview:
Thyroid receptor (TR) regulates many homeostatic processes including basal metabolism, cardiovascular function, body weight, and lipid trafficking. TR modulators are potential therapeutics for obesity and hyperlipidemias but current thyroid analogs have undesirable side effects, particularly cardiac stimulation. This secondary assay characterized compounds identified in the qHTS for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2 (PubChem AID 1485) for selectivity against the androgen receptor (AR). This assay detects interaction of the ligand-binding domain of human AR with a Texas Red labeled SRC2-3 peptide, corresponding to a 20 amino acid region of the nuclear receptor interaction domain. Small molecule inhibitors that block the interaction of AR and SRC2-3 are detected by a decrease in fluorescence polarization.
Protocol
NCGC Assay Protocol Summary:
Twenty uL/well 1 uM liganded AR-LBD and 10 nM Tx-SRC2-3 peptide in buffer (50 mM HEPES, 150 mM Li2SO4, 0.2mM TCEP, 10% glycerol, pH 7.2, and 4% DMSO) was dispensed into black solid 384-well plates (Costar 3710) using a Biomek FX (Beckman Coulter) liquid handling system. Following transfer of 260 nL compound (ranging from 7 nM to 130 uM), the plates were incubated 3 hr at ambient temperature. The plates were read by an Envision (Perkin Elmer) to detect Texas Red polarization of Tx-SRC2-3 (555 nm excitation and 632 nm emission).
Twenty uL/well 1 uM liganded AR-LBD and 10 nM Tx-SRC2-3 peptide in buffer (50 mM HEPES, 150 mM Li2SO4, 0.2mM TCEP, 10% glycerol, pH 7.2, and 4% DMSO) was dispensed into black solid 384-well plates (Costar 3710) using a Biomek FX (Beckman Coulter) liquid handling system. Following transfer of 260 nL compound (ranging from 7 nM to 130 uM), the plates were incubated 3 hr at ambient temperature. The plates were read by an Envision (Perkin Elmer) to detect Texas Red polarization of Tx-SRC2-3 (555 nm excitation and 632 nm emission).
Comment
Compound Ranking:
All compounds were inactive and were assigned a score of 0.
All compounds were inactive and were assigned a score of 0.
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Activity | Indicates type of activity observed: active or inactive. | String | |||
| 2 | Potency* | The concentration of sample yielding half-maximal inhibition. |  | Float | μM | |
| 3 | Compound QC | NCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling' | String |
* Activity Concentration.
Additional Information
Grant Number: DK058080
Data Table (Concise)
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