# GPR88 Agonist for Alcoholism Treatment

> **NIH NIH R01** · RESEARCH TRIANGLE INSTITUTE · 2022 · $516,567

## Abstract

Project Summary
 The goal of this project is to develop GPR88 agonists to treat alcohol use disorders.
Alcoholism is a heterogeneous, chronic relapsing disorder. Available medications to treat alcoholism have
limited efficacy, serious side effects, and compliance issues. Therefore, new medications based on novel
targets are needed. The orphan receptor GPR88 is a G-protein-coupled receptor with robust expression in the
striatum throughout the dorsal and ventral areas. Multiple lines of evidence suggest that GPR88 plays an
important role in the regulation of striatal functions and is implicated in alcohol-seeking behaviors. Our
preliminary results in behavioral studies using GPR88 knockout mice and a selective GPR88 agonist support
the hypothesis that GPR88 agonism is beneficial to treat alcohol addiction and dependence. Based on the
research conducted in our probe project R21 MH103708, we have developed the first potent, selective, and
brain-penetrant small molecule GPR88 agonists. In this application, we propose to refine our early lead
compounds to produce GPR88 agonists for in vivo studies through three iterative specific aims. In Aim 1, we
will optimize potency, receptor selectivity, and drug-like properties of GPR88 agonists using medicinal
chemistry. In Aim 2, we will characterize compounds using GPR88 functional assays (cAMP and GTPS
binding assays). Potent compounds will then be characterized using a battery of ADMET and pharmacokinetic
assays. In Aim 3, we will evaluate the efficacy of select compounds, developed in Aims 1 and 2, in animal
models of alcohol drinking and reinforcement. Overall, completion of this project will provide in vivo probes to
further characterize the GPR88 system and pharmacologically validate GPR88 as a novel target for treatment
of alcoholism.

## Key facts

- **NIH application ID:** 10459403
- **Project number:** 5R01AA026820-05
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **Principal Investigator:** Chunyang Jin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $516,567
- **Award type:** 5
- **Project period:** 2018-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459403

## Citation

> US National Institutes of Health, RePORTER application 10459403, GPR88 Agonist for Alcoholism Treatment (5R01AA026820-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10459403. Licensed CC0.

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