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A Tool for Modeling the Structure-Activity of Chemokine Receptors and Other GPCRs

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44GM076779-02
Agency Tracking Number: GM076779
Amount: $775,397.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: 2007
Award Year: 2007
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
INTEGRAL MOLECULAR 3701 MARKET ST, STE 340
PHILADELPHIA, PA 19104
United States
DUNS: 034055645
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 BENJAMIN DORANZ
 (215) 966-6018
 bdoranz@integralmolecular.com
Business Contact
 BENJAMIN DORANX
Phone: (215) 966-6018
Email: BDORANZ@INTEGRAL MOLECULAR.COM
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): Understanding the precise molecular interactions between drugs and their targets, their structure-activity relationship (SAR), is a highly desirable goal during drug development. GPCRs are the single largest family of drug targets in the pharmaceutical industry, yet structural information about them is exceptionally difficult to obtain. The product that will arise from this proposal, the Structure-Activity Relationship Array (SARray), will enable structural interactions of GPCRs with drug candidates and other ligands to be determined at molecular resolution. We have demonstrated the feasibility of constructing SARrays and of using them to obtain useful structural information. We identified the structural determinants of five different CCR5 molecular interactions, including critical amino acids responsible for interacting with a chemokine (RANTES), two monoclonal antibodies (2D7 and 45523), HIV-1 Env (JRFL), and a small- molecule drug (TAK-779). Our results were validated against and agree with published results. The Specific Aims of our Phase 2 proposal are: I. Test the ability of SARray data to predict detailed receptor-ligand interactions II. Develop structure-activity analysis tools and data management software. III. Create SARrays for validated GPCR drug targets The product that results from this proposal will contribute to human health by facilitating the optimization and design of drugs targeted to GPCRs. Understanding the precise molecular interactions between drugs and their targets, their structure-activity relationship (SAR), is a highly desirable goal during drug development. GPCRs are the single largest family of drug targets in the pharmaceutical industry, yet structural information about them is exceptionally difficult to obtain.

* Information listed above is at the time of submission. *

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