Small molecules Manipulation of G Protein Subunit Signaling for Chronic Pain Management and Opioid-Tolerance

Brief Description

Applications:

Researchers at the University of Rochester have developed as assay to identify compounds targeting the downstream effectors to which GPCRs are coupled and elicit specific biological responses (i.e., the G-proteins alpha and ßgamma).  Targeting the G-proteins' messengers presents a therapeutic advantage since has greater efficacy and enhancement of selectivity. More specifically, compounds which disrupt the ability of Gßgamma to activate subsequent effectors in a particular GPCR-mediated signaling pathway.  As such, small molecule inhibition of Gßgamma represents a significant means for the treatment of a number of GPCR-related pathological conditions, including chronic pain resulting from opioid tolerance.

The assay has identified multiple high-affinity compounds which can block distinct Gßgamma functions, including in vito  protein-protein interactions and related biological signaling responses in intact cells and animal models. This platform technology can serve as an expansive drug discovery engine, potentially yielding proprietary therapeutics with novel mechanisms of action. 

Specifically, new compounds were identified which block the development of opioid tolerance, and prevent opiate withdrawal when co-administered with morphine.

 

Advantages:

Small molecule inhibition of specific aspects of Gßgamma-dependent signaling offers a powerful and yet-to-be exploited therapeutic strategy with multiple applications and advantages. A new class of combination therapeutics may be developed where the effective dose of opiates can be reduced and problems of dependence and tolerance are avoided.

Patent Information:
Title Country Patent No. Issued Date
Methods for Treating Opioid Tolerance United States 8,748,480 6/10/2014
Category(s):
Therapeutic
For Information, Contact:
Matan Rapoport
Licensing Associate
University of Rochester
585.276.6600
matan.rapoport@rochester.edu
Inventors:
Alan Smrcka
Jose Font
Tabetha Bonacci
Keywords:
Anti-inflammatory
Autoimmune
Cardiovascular
Immunology
Inflammation
Receptor
Small Molecule
Target Validation
Therapy