# Small molecule inhibitors of TrkB Signaling

> **NIH NIH R61** · DUKE UNIVERSITY · 2024 · $411,928

## Abstract

Project Summary/Abstract
 Temporal lobe epilepsy (TLE) is a common and commonly devastating form of human epilepsy that lacks
preventive or disease modifying therapy. An estimated 30% suffer recurrent seizures despite symptomatic
treatment with anticonvulsants. One cause of TLE is status epilepticus (SE). Defining the molecular
mechanisms by which SE induces TLE promises to identify molecular targets for therapies. We therefore
conducted extensive target validation experiments which revealed TrkB-PLCγ1 as a druggable molecular
target that can prevent TLE in adult mice. The goal of our drug discovery program is to develop small molecule
inhibitors for TrkB-PLCγ1 signaling to treat TLE. With the support of Blueprint Neurotherapeutics Network
(BPN), we identified multiple compounds within distinct series with demonstrated in vivo efficacy for inhibition
of TrkB-PLCγ1 signaling in mouse brain. Our Specific Aims are to benchmark, expand, and optimize novel
small molecule inhibitors of TrkB-PLCγ1 signaling. Successful completion of the work proposed will identify a
leading series for entry to the Discovery Phase of BPN program.

## Key facts

- **NIH application ID:** 10917401
- **Project number:** 5R61NS133213-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** James O. McNamara
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,928
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917401

## Citation

> US National Institutes of Health, RePORTER application 10917401, Small molecule inhibitors of TrkB Signaling (5R61NS133213-02). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10917401. Licensed CC0.

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