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
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.
assay has identified multiple high-affinity compounds which can block distinct
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.
new compounds were identified which block the development of opioid tolerance,
and prevent opiate withdrawal when co-administered with morphine.
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.