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BioAssay: AID 504856

Inhibitors of Regulator of G Protein Signaling (RGS) 4: Summary

G-protein-coupled receptors (GPCRs) are well-established targets for drug discovery and development. Members of the "regulator of G-protein signaling" (RGS)-protein superfamily have recently emerged as critical modulators of specific GPCR signaling pathways. Via their conserved RGS domain that possesses "GTPase-accelerating protein" (GAP) activity, RGS proteins deactivate heterotrimeric G-protein more ..
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AID: 504856
Data Source: NCGC (RGS4000)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-06-27
Target
Related Experiments
AIDNameTypeComment
504845Inhibitors of Regulator of G Protein Signaling (RGS) 4: qHTSConfirmatorydepositor-specified cross reference
602388qHTS for Inhibitors of Regulator of G Protein Signaling(RGS) 4: Hit ValidationConfirmatorydepositor-specified cross reference
Description:
G-protein-coupled receptors (GPCRs) are well-established targets for drug discovery and development. Members of the "regulator of G-protein signaling" (RGS)-protein superfamily have recently emerged as critical modulators of specific GPCR signaling pathways. Via their conserved RGS domain that possesses "GTPase-accelerating protein" (GAP) activity, RGS proteins deactivate heterotrimeric G-protein alpha (G) subunits and thus attenuate GPCR signal transduction. Combining specific RGS domain inhibitors with existing GPCR agonists should potentiate cellular responses and could also increase the specificity of action of existing therapeutics. Small molecule modulators of RGS domain activity should also have clinical utility in inhibiting or potentiating the actions of endogenous GPCR agonists. In particular, the diversity of RGS proteins with highly localized and dynamically regulated distributions in the human brain makes this family of proteins attractive targets for pharmacotherapy of central nervous system (CNS) disorders such as Parkinson's disease, schizophrenia, and anxiety.

Hence, in a collaboration between the University of North Caroline Chapel Hill (School of Medicine) and NIH Chemical Genomics Center (NCGC) a novel HTS-compatible enzymatic assay for RGS-accelerated GDP production was developed. This assay was used to screen the NIH Molecular Libraries Small Molecule Repository (MLSMR) in order to identify a small molecule that inhibits RGS4. Several follow-up assays have also been developed, please linked AIDs for more information.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: DA030555-01
Assay Submitter (PI): David Siderovski, University of North Carolina Chapel Hill (School of Medicine)
Protocol
Please see linked AID for a detailed protocol for each assay.
Comment
This project is on-going and will be updated at a later point with findings.
Additional Information
Grant Number: DA030555

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