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BioAssay: AID 485359

HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Antagonists Summary

Dopamine receptors (DARs) are involved in the etiology and/or therapy of a number of neuropsychiatric and endocrine disorders. For instance, all receptor-based antiparkinsonian drugs work via stimulating the D2 DAR subtype whereas all FDA-approved antipsychotic agents are antagonists of this receptor. Most drugs targeting the D2 DAR are problematic, however, either being less efficacious as more ..
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AID: 485359
Data Source: NCGC (DOP2302)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2010-10-05
Target
Related Experiments
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AIDNameTypeComment
485344HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Primary Screen for AntagonistsScreeningdepositor-specified cross reference: Primary antagonist screen.
485347HTS Assay for Positive Allosteric Modulators of the Human D2 Dopamine Receptor: Primary Screen for PotentiatorsScreeningdepositor-specified cross reference: Primary potentiator counterscreen.
624453HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Hit Validation in primary assayConfirmatorydepositor-specified cross reference
624455HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Hit Validation in HTRFConfirmatorydepositor-specified cross reference
624459HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Hit Validation in Parental Cell LineConfirmatorydepositor-specified cross reference
624461HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: Hit Validation in Radioligand AssayOtherdepositor-specified cross reference
624494HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: SAR in D2 Binding AssayOtherdepositor-specified cross reference
624495HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: SAR in D2 Beta Arrestin AssayConfirmatorydepositor-specified cross reference
624496HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: SAR in Primary Assay.Confirmatorydepositor-specified cross reference
624500HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: SAR in D3 Beta Arrestin AssayConfirmatorydepositor-specified cross reference
624502HTS Assay for Allosteric Antagonists of the Human D2 Dopamine Receptor: SAR in D3 Binding AssayOtherdepositor-specified cross reference
Description:
NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: NS064831-01
Assay Submitter (PI): David Sibley

Dopamine receptors (DARs) are involved in the etiology and/or therapy of a number of neuropsychiatric and endocrine disorders. For instance, all receptor-based antiparkinsonian drugs work via stimulating the D2 DAR subtype whereas all FDA-approved antipsychotic agents are antagonists of this receptor. Most drugs targeting the D2 DAR are problematic, however, either being less efficacious as desired or possessing limiting side effects, most of which are due to reactivity at other receptors. One approach towards improved receptor specificity is to identify allosteric ligands that bind to less conserved regions of the receptor and therefore have the potential to be much more selective. The goal of this project is to use high throughput screening approaches to identify and develop novel, highly selective small molecule allosteric modulators of the D2 DAR for use as in vitro and in vivo pharmacological tools and in proof-of-concept experiments in animal models of neuropsychiatric disease. There are three different types of allosteric modulators that we are seeking, two of which will stimulate or augment receptor signaling, allosteric agonists and potentiators, while the third, allosteric antagonists, will attenuate receptor signaling. The present project is looking for compound antagonism after an EC80 addition of dopamine by tracking calcium flux in a force-coupled, inducible Hek293 Trex D2 cell line, which act through an allosteric site.
Protocol
See related assays for detailed assay protocols.
Comment
Keywords: NIH Roadmap, MLSCN, MLI, MLSMR, qHTS, NCGC
Compound ranking comments will be provided here as small molecule probes are developed and are updated with results in PubChem.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML321
PubChem Substance ID (SID) for probe 1: 136882616
PubChem Compound ID (CID) for probe 1: 57377246
Probe type for probe 1: Antagonist
IC50/EC50 (nM) for probe 1: 120
Target for probe 1: D2 DAR receptor (gi: 4503385)
Disease relevance for probe 1: Neurological disease
Anti-target for probe 1: D3 DAR receptor
Fold selectivity for probe 1: 17
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK169449/ (ID: 3060638)
Grant number for probe 1: NS064831
PubMed Publication ID (PMID) for probe 1: 24666157
NCBI Book chapter title for probe 1: Discovery, optimization, and characterization of a novel series of dopamine D2 versus D3 receptor selective antagonists
Additional Information
Grant Number: NS064831-01

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