# Quantitative and computational characterization of oxytocin receptor signaling: Administrative supplement

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $279,477

## Abstract

PROJECT SUMMARY
In the US, nearly half of all pregnant women are treated with a synthetic version of the neuropeptide oxytocin to
induce or augment labor or prevent postpartum hemorrhage. However, women require a wide range of oxytocin
doses to elicit an appropriate degree of uterine contractility. Furthermore, the oxytocin receptor (OXTR) can
cease to respond to oxytocin (become desensitized) after long-term oxytocin administration, often leading to the
need for cesarean delivery. Failure of OXTR activation can lead to substantial maternal morbidity and, in extreme
cases, mortality due to postpartum hemorrhage. Our long-term goal is to develop strategies to improve OXTR
responsiveness and thereby improve safety for pregnant women. In our parent grant, we hypothesized that
OXTR genetic variants are contributing to the observed differences in individual response to oxytocin and
propose to quantitate these effects in order to build a computational model able to predict response. In this
supplement, we propose to develop a new approach for regulation of OXTR activity by identifying and
characterizing OXTR positive allosteric modulators (PAMs). OXTR PAMs would be ideal therapeutics because
they do not activate their target receptor in the absence of an agonist. Instead, they enhance endogenous ligand
activity by binding to the receptor outside of the native ligand binding site. Thus, OXTR PAMs would
predominantly enhance OXTR activation in the uterus, where oxytocin concentration is highest, and follow the
same temporal OXTR activation pattern brought about by pulsatile oxytocin release during labor. We will pursue
two Specific Aims: 1) Identify and validate positive allosteric modulators of OXTR, and 2) Determine how the
top hit compounds enhance OXTR signaling. In order to identify the PAMs, we will perform a large-scale screen
of diverse small-molecule compounds. In characterizing PAM effects on OXTR signaling, we will also obtain
quantitative data to enhance our computational approaches. Together, data from the funded R01 and this
supplement will lead to individualized oxytocin administration and an alternative pharmacologic approach to
activate OXTR to induce or augment labor.

## Key facts

- **NIH application ID:** 10175765
- **Project number:** 3R01HD096737-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sarah K. England
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $279,477
- **Award type:** 3
- **Project period:** 2019-08-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175765

## Citation

> US National Institutes of Health, RePORTER application 10175765, Quantitative and computational characterization of oxytocin receptor signaling: Administrative supplement (3R01HD096737-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10175765. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*