# Identification of small molecule NPBWR1 agonists

> **NIH NIH R03** · RESEARCH TRIANGLE INSTITUTE · 2024 · $120,166

## Abstract

Abstract
Chronic pain is one of the leading health problems worldwide. Opioids have served as gold standard for
treating moderate to severe pain. However, opioids possess serious adverse effects that limit their use in
clinics. Therefore there is an unmet need for alternative effective and non-addictive pain treatments.
Neuropeptide B/W Receptor 1 (NPBWR1) has emerged as a novel pain target which upon activation can
produced analgesic effects on its own or in synergy with opioids. To date, all reported NPBWR1 agonists
are peptides or peptidomimetics that do not cross the blood brain barrier, requiring central administration.
To facilitate research on this promising target, we propose to perform a high throughput screen of our
diverse small molecule library to identify small molecule agonists (Aim 1). We have developed a battery of
in vitro functional assays to characterize NPBWR1 ligands including a cAMP, calcium mobilization and
TruPath assays. The 384-well cAMP assay has been demonstrated to have good robustness Z'>0.5, S/B >
20. Hits will be validated using counter screen and orthogonal assays. Validated hits will be assessed for
ADME profiling and selectivity against other targets (Aim 2). Completion of this proposal will yield small
molecule NPBWR1 that serve as starting points for subsequent medicinal chemistry optimization to develop
into therapeutics for chronic pain and other NPBWR1-mediated conditions.

## Key facts

- **NIH application ID:** 10904943
- **Project number:** 5R03DA058800-02
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **Principal Investigator:** Ann M Decker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $120,166
- **Award type:** 5
- **Project period:** 2023-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904943

## Citation

> US National Institutes of Health, RePORTER application 10904943, Identification of small molecule NPBWR1 agonists (5R03DA058800-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10904943. Licensed CC0.

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