# Lipid Receptor GPR31 as a Target for Anti-Thrombotic and Stroke Therapy

> **NIH NIH R42** · OASIS PHARMACEUTICALS · 2024 · $999,799

## Abstract

Despite prevalent use of anti-platelet and anti-lipid therapies, stroke remains the third major cause of death
and is the leading cause of adult disability in the US with an estimated cost in the range of $34 billion
annually. Approximately 20% of the annual 795,000 stroke patients die within one year and 15-30% are
permanently disabled. Antiplatelet therapy is mainly used for primary prevention of acute ischemic stroke in
cerebrovascular disease. Bioactive fatty acids are a new class of molecular targets that hold great
therapeutic potential because of their diverse role as signaling molecules that regulate metabolism and
inflammation. The oxidation of arachidonic acid by 12-LOX results in the production of a number of bioactive
lipids including the metabolite 12(S)-HETE. The lipid receptor GPR31, an orphan class A GPCR, is a 12(S)-
HETE receptor recently shown to be involved in inflammatory signaling. We recently discovered that GPR31
mediates 12(S)-HETE prothrombotic signaling in platelets and promotes glutamate-induced oxidative
toxicity in neuronal cells. Therefore, we propose that targeting GPR31 may provide a therapeutic path
towards development of a safe and effective antiplatelet therapy that is coupled with secondary
neuroprotective effects for mitigating against the acute neurologic sequela of stroke to provide a more
effective and safer alternative option or adjunct to fibrinolytic therapy. We have recently succeeded in
identifying the first effective GPR31 antagonist using our cell-penetrating, membrane-tethered, Pepducin
technology to be validated in these preclinical IND-enabling studies as an anti-platelet and anti-stroke
agent. We show here that this i3-loop derived GPR31 lipopeptide has potent antiplatelet activity and nearly
completely suppresses arterial thrombosis without an effect on hemostasis in mice. Preliminary data with
the GPR310 pepducin shows a highly significant reduction in stroke infarct area in mice similar to the
protective effect of Gpr31-deficiency. Furthermore, we provide evidence for a direct neuroprotective effect of
the GPR310 pepducin on HT22 neuronal cells subjected to glutamate mediated oxidative stress. The goal
of this Phase 2 STTR project is to develop the GPR310 pepducin as a collaborative effort between Oasis
Pharmaceuticals (Lexington, MA), Tufts Medical Center (Boston, MA) that would provide a robust IND data
package required to advance the initial commercial development of the first GPR31 inhibitor as a dual
antiplatelet, anti-stroke drug. This drug development program would establish the scientific merit of the
GPR31 target by accomplishing the major milestones at the end of 2 years of GLP safety/pharmacology
and efficacy in stroke models ± thrombolytic therapy to support a Phase I first-in-human clinical trial.

## Key facts

- **NIH application ID:** 10765721
- **Project number:** 5R42HL160429-03
- **Recipient organization:** OASIS PHARMACEUTICALS
- **Principal Investigator:** Athan Kuliopulos
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $999,799
- **Award type:** 5
- **Project period:** 2023-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765721

## Citation

> US National Institutes of Health, RePORTER application 10765721, Lipid Receptor GPR31 as a Target for Anti-Thrombotic and Stroke Therapy (5R42HL160429-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10765721. Licensed CC0.

---

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