# Development of ferroptosis inhibitors for Huntington Disease

> **NIH NIH R33** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2022 · $388,068

## Abstract

Project Summary
Ferrostatin is a potent inhibitor of ferroptosis; which is a non-apoptotic form of cell death potentially involved in
a number of degenerative diseases. We have shown the effectiveness of Fer-1 in brain slice models of
Huntington's disease (HD) and glutamate toxicity. However, ferrostatin's pharmacokinetic/pharmacodynamic
(PK/PD) properties make it unsuitable for use in animal models to further test the role of ferroptosis in these
diseases. We have made a series of ferrostatin analogs to explore ferrostatin's structure-activity relationship
(SAR) and to improve activity and metabolic and plasma stability. While we have made significant progress in
creating metabolically stable analogs with good potency and plasma stability, additional improvements are
envisioned that could result in highly potent, stable compounds that could be dosed in vivo. The result of this
investigation will be a set of optimized compounds for in vivo use to study the role of lipid peroxidation in a
mouse model of Huntington Disease. In the longer term, we will be able to use these optimized compounds to
probe the role of lipid peroxidation and ferroptosis in a variety of degenerative diseases.

## Key facts

- **NIH application ID:** 10461960
- **Project number:** 5R33NS109407-03
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Brent R. Stockwell
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,068
- **Award type:** 5
- **Project period:** 2021-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461960

## Citation

> US National Institutes of Health, RePORTER application 10461960, Development of ferroptosis inhibitors for Huntington Disease (5R33NS109407-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10461960. Licensed CC0.

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