# Repurposing CRH antagonists for the treatment of endometriosis

> **NIH NIH R41** · SUR180 THERAPEUTICS, LLC · 2022 · $299,864

## Abstract

PROJECT SUMMARY
Endometriosis is a chronic condition that affects 10% of reproductive-aged women worldwide. Unfortunately, up
to 59% of women with endometriosis do not respond to the available treatments and continue to suffer from
endometriosis-associated pain or recurrent pain after treatment cessation. Therefore, treatment alternatives that
deviate from the current therapeutic focus are urgently needed. The corticotrophin-releasing hormone receptor
type 1 (CRHR1) is a largely unexplored target. Corticotropin-releasing hormone (CRH), which activates the
CRHR1, is a critical molecule in the hypothalamic-pituitary-adrenal (HPA) axis that integrates stress and
endocrine responses both in the brain and in peripheral tissues. CRHR1 is abundant in the endometrium and
ovaries and has a role in developing endometriotic tissues, as demonstrated by the team's previous work.
CRHR1 antagonists were introduced into clinical trials for mood and gastrointestinal disorders with little to no
effect on those diseases and have never reached approval for commercial use. Previous work from the research
team demonstrated that short-term treatment with antalarmin, a CRHR1 antagonist frequently used in pre-clinical
experimentation, showed a 30% decrease in endometriosis development and a 60% decrease in the weight and
size of endometriosis vesicles. In continuation of these efforts, the overarching goal is to develop and
commercialize CRHR1 antagonists to treat endometriosis. The research team will focus on a compound recently
out of patent and reached Phase 2 clinical trials but was not effective for depression, anxiety, or alcoholism. To
begin addressing our goal, two specific aims were designed: on Aim 1, we will determine the effectiveness of a
clinically relevant CRHR1 antagonist for endometriosis treatment, including its effectiveness in decreasing
associated pain. Aim 2 will determine whether the CRHR1 antagonist affects the gonadal axis's cyclic hormonal
activity, independent of antiproliferative activity. Both aims will be done using the well-established
autotransplantation rat model of endometriosis, allowing for effective quantification and characterization of
endometriotic vesicles. Completed aims will reveal the optimal intervention for halting endometriosis progression
and predict possible mechanisms of action directly associated with the role of CRHR1 in the gonadal system.
Future efforts will focus on how the CRHR1 antagonism impacts fertility and fecundity, which are critical factors
to apply for re-introduction into clinical testing at the FDA. Bringing CRHR1 antagonists into the commercial field
have the strong potential of decreasing surgical interventions in women with endometriosis, resulting in
thousands of dollars saved in healthcare and indirect costs. The research team has identified the potential to
repurpose CRHR1 antagonists, but before being re-introduced into clinical trials, additional proof of action and
pre-clinical effectiveness is n...

## Key facts

- **NIH application ID:** 10602801
- **Project number:** 1R41HD109055-01A1
- **Recipient organization:** SUR180 THERAPEUTICS, LLC
- **Principal Investigator:** Caroline B Appleyard
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $299,864
- **Award type:** 1
- **Project period:** 2022-09-19 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10602801

## Citation

> US National Institutes of Health, RePORTER application 10602801, Repurposing CRH antagonists for the treatment of endometriosis (1R41HD109055-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10602801. Licensed CC0.

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