USA flag logo/image

An Official Website of the United States Government

GIR Antagonists: Novel Feeding/Catabolism Molecules

Award Information

Department of Health and Human Services
Award ID:
Program Year/Program:
2005 / SBIR
Agency Tracking Number:
Solicitation Year:
Solicitation Topic Code:
Solicitation Number:
Small Business Information
10101 Alliance Rd CINCINNATI, OH 45242-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Phase 1
Fiscal Year: 2005
Title: GIR Antagonists: Novel Feeding/Catabolism Molecules
Agency: HHS
Contract: 1R43DK074306-01
Award Amount: $174,407.00


DESCRIPTION (provided by applicant): Obesity has risen to epidemic proportions in the United States, contributing to over 52 billion USD per year in direct medical costs. Limited treatment options and significant side effects of currently used Pharmaceuticals necessitate the search for new and better pharmaceutical targets. P2D, Inc. has developed for immediate testing, non-peptide small molecule antagonists of a novel feeding target, glucocorticoid-induced receptor (GIR; GPCR 83). GIR is a neuropeptide Y-like receptor that binds anorectic peptide PYY3-36 as well as synthetic peptide T-100. Preliminary studies of the lead compound, T-100 (US patents 6013633 & 6235718 Bl), demonstrate that T-100 significantly attenuates food intake in rats using different feeding paradigms. This Phase 1 SBIR will test non-peptide small molecules, PD1-PD10, derived from T-100 structure-activity assessment of the GIR pharmacophore. First, compounds will be tested for GIR binding and antagonism of GIR-mediated signal transduction via phospho-CREB. The most potent of these small molecule GIR antagonists will then undergo in vivo testing with a goal to achieve the 80% reduction of feeding seen with T-100, with better CNS penetration and bioavailability properties. These goals will be achieved under the following Aims, Specific Aim 1: Compounds PD1 through PD10 will be tested for biological activity in vitro using a cell line (GIRD7) that expresses the novel NPY-like receptor GIR. Compounds PD1 to PD10 will be tested for binding to GIR expressed in GIRD7 cells by competition assays and for antagonism of pCREB- induced luciferase activation mediated by GIR in GIRD7 cells. Efficacy of non-peptide compounds for binding and functional antagonism of GIR will be compared to that observed for peptide antagonist T-100. Specific Aim 2: In vivo testing of drug candidates in animal models of feeding behavior and energy expenditure. The three most potent candidates (as determined by Specific Aim 1) will be tested in rats for effects on food intake, energy expenditure, conditioned taste aversion. CNS penetration and dose- response behavior will be evaluated in two routes of administration, intracerebroventricular (i.c.v). vs. intraperitoneal (i.p.) T-100 will be employed as a positive control.

Principal Investigator:

Somasundar P. Gabbita

Business Contact:

Small Business Information at Submission:

P2D, Inc.
P2D, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, OH 45219

EIN/Tax ID: 202224724
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No