USA flag logo/image

An Official Website of the United States Government

HTS Assays for Modulators of GPCR Signaling

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85927
Program Year/Program:
2007 / SBIR
Agency Tracking Number:
NS059082
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
BELLBROOK LABS, LLC
5500 NOBEL DR, STE 230 MADISON, WI -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2007
Title: HTS Assays for Modulators of GPCR Signaling
Agency: HHS
Contract: 1R43NS059082-01
Award Amount: $235,189.00
 

Abstract:

DESCRIPTION (provided by applicant): More than 50% of drugs on the market target G protein-coupled receptors (GPCRs). Among the most important of these are drugs used to treat neurological disorders, such as pain relievers, antidepressants and anti-psychot ics, as well drugs used for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The relatively recent discovery of a family of proteins called regulator of G protein signaling (RGS), that attenuate GPCR signals by increasing t he GTPase activity of associated Ga proteins, has opened up a new avenue for modulating the activity of endogenous and administered GPCR ligands. However, development of inhibitors to RGS proteins has been hampered by the lack of robust assay methods for h igh throughput screening (HTS). To overcome this technical hurdle, we propose to use fluorescence based immunodetection of GDP to measure RGS-dependent increases in the steady state GTPase activity of modified Ga proteins. Based on the approach used previo usly at BellBrook Labs for development of an ADP detection assay, a highly specific monoclonal antibody and fluorescent tracer will be developed for detection of GDP. The Ga proteins will be mutated to increase the rate of GDP dissociation relative to GTP hydrolysis so that the former is no longer rate limiting. The availability of these novel HTS assays will accelerate drug discovery focused on RGS proteins and delineation of their roles in GPCR signal transduction. Over half of current drugs exert their e ffects through a family of proteins called G protein- coupled receptors, and the targeting of these receptors has been especially useful for the development of drugs used to treat neurological disorders such as schizophrenia, depression, and Parkinson's di sease. To accelerate discovery of more selective therapies for these and other diseases, we are developing novel screening assays for a family of proteins, called 'regulator of G-protein signaling' (RGS) that modulate the effects of GPCR ligands in a tissu e-specific manner.

Principal Investigator:

Robert G. Lowery
6082274501
BOB.LOWERY@BELLBROOK-LABS.COM

Business Contact:

Robert G. Lowery
bob.lowery@bellbrooklabs.com
Small Business Information at Submission:

BELLBROOK LABS, LLC
5500 Nobel Drive Suite 250 MADISON, WI 53711

EIN/Tax ID: 043661356
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No