# Testing the Lipoxygenase Inhibitor BPN-27332 as Acute Phase Stroke Treatment in the SPAN Network

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $312,234

## Abstract

The goal of this project is to evaluate a novel inhibitor of the 12/15 lipoxygenase (12/15-LOX) enzyme in
preclinical rodent models of ischemic stroke within the SPAN network. To this end, BPN-27332 will be tested in
comparison with other preclinical stroke treatments under rigorous conditions in multiple laboratories.
12/15-LOX has been shown to be up-regulated in the ischemic peri-infarct area in both rodents and humans. It
contributes to both neuronal cell death, as well as to weakening of the blood – brain barrier and edema
formation. Alox15(-/-) mice in which the gene encoding 12/15-LOX has been knocked out, are protected in
models of transient focal ischemia. Through the NIH Blueprint Neurotherapeutics Program we have developed
BPN-27332, a novel and highly selective inhibitor of 12/15-LOX. In a mouse model of transient focal ischemia,
BPN-27332 reduces infarct size when given in the acute phase. Protection is long lasting, with significant
behavioral benefits still seen four weeks after the experimental stroke with excellent ADME and PK/PD
properties. We now propose to test BPN-27332 in a blinded fashion in comparison with vehicle, but also with
other treatment modalities. In Aim 1, the compound is subjected to rigorous quality control measures, including
verification of identity and purity by HPLC and mass spectrometry and in vitro efficacy testing. In Aim 2, the
compound will be shipped to the Coordinating Center for distribution to the testing sites, where BPN-27332 will
be extensively tested in rodent models of ischemic stroke. Successful completion of these studies will ready
BPN-27332 for clinical trials in human patients, which will hopefully lead to a much needed new treatment
option for patients with ischemic strokes.

## Key facts

- **NIH application ID:** 10832631
- **Project number:** 5U01NS132332-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** KLAUS VAN LEYEN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $312,234
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832631

## Citation

> US National Institutes of Health, RePORTER application 10832631, Testing the Lipoxygenase Inhibitor BPN-27332 as Acute Phase Stroke Treatment in the SPAN Network (5U01NS132332-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10832631. Licensed CC0.

---

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