# Molecular Determinants for GPR55 Activity

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $344,175

## Abstract

GPR55 is a lysophosphatidylinositol (LPI)-sensitive G-protein coupled receptor (GPCR) that recognizes a sub-
set of cannabinoid CB1 and CB2 ligands. The goal of the proposed project is to understand the functional
features of GPR55 that may define mechanisms of drug-receptor interactions relevant to physiological and
pathophysiological function, including drug abuse. GPR55 has been implicated in inflammatory pain,
neuropathic pain, metabolic disorder, bone and neurological development, and cancer, indicating the real
potential of GPR55 ligands as therapeutics. Each of these areas alone is medically important and each would
benefit by the use of selective agonists and antagonists to further studies. While selective agonists and
antagonists for GPR55 from a number of diverse scaffolds have been identified, no low nanomolar potency
ligands have been confirmed for this receptor, nor is there a radioligand developed to characterize binding. We
have recently identified the first set of GPR55 residues important for agonist signaling and for GPR55
activation. This information should aid in the rational design of next generation GPR55 ligands, using our
evolving molecular model. The goal of this proposal is to use structure-based design and cheminformatics
tools to develop structure-activity relationships for selected scaffolds, leading to the identification of low
nanomolar ligands that retain high receptor selectivity. We aim to discover nanomolar potency GPR55 ligands
using a combination of molecular modeling, chemoinformatics, high-throughput screening and site directed
mutagenesis. We will dissect the specific signaling pathways governing GPR55 activity as well as investigate
ligand bias.

## Key facts

- **NIH application ID:** 9891998
- **Project number:** 5R01DA045698-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** MARY E ABOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,175
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891998

## Citation

> US National Institutes of Health, RePORTER application 9891998, Molecular Determinants for GPR55 Activity (5R01DA045698-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9891998. Licensed CC0.

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