# Effects of a G protein signaling-biased mu opioid receptor agonist SR-17018 in primates

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $205,966

## Abstract

Mu opioid peptide (MOP) receptor agonists such as morphine and fentanyl are the most
widely used analgesics for pain management. However, MOP receptor agonist-induced
respiratory depression and mortality lead to mounting medical and economic burdens in
the global community. Recent evidence indicates that biased MOP receptor agonists
with preferred G protein activation retained analgesic effects, but they produced wider
therapeutic windows. Such G protein signaling-biased MOP receptor agonists have not
been systemically studied in non-human primate (NHP) models with translational
potential. In this application, we select a newly discovered G protein signaling-baised
MOP receptor agonist with the highest bias factor, SR-17018, which will be synthesized
by Dr. Yanan Zhang at Research Triangle Institute. A series of NHP experiments will be
conducted to evaluate behaivoral and physiological effects of SR-17018 in side-by-side
comparisons with clinically used MOP receptor agonists following acute and repeated
administration. These NHP assays have been designed specifically to reflect the
therapeutic (analgesia) and side effects (respriatory depression, abuse potential,
constipation, physical dependence, and tolerance) of opioid analgesics. The possibility
that biased MOP receptor agonists which do not recruit beta-arrestin may be safer and
have a wider therapeutic window encourages our pharmacological studies of SR-17018
in NHP models. Our unique set of behavioral and physiological assays in awake,
behaving rhesus monkeys, in combination with the availability of a novel, highly G
protein-biased MOP receptor agonist, SR-17018, sets the breakthrough stage for the
identification of safer opioid analgesics in primates and sheds light on future clinical
interventions with such novel opioid analgesics.

## Key facts

- **NIH application ID:** 10120663
- **Project number:** 5R21DA049580-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MEI-CHUAN KO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,966
- **Award type:** 5
- **Project period:** 2020-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120663

## Citation

> US National Institutes of Health, RePORTER application 10120663, Effects of a G protein signaling-biased mu opioid receptor agonist SR-17018 in primates (5R21DA049580-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120663. Licensed CC0.

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