# Target identification of small molecule LDN/OSU-215111

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $456,800

## Abstract

Glutamate transporter EAAT2 plays a critical role in the homeostatic regulation of extracellular
glutamate levels. EAAT2 also plays an essential role in cognitive memory functions. However, loss of
EAAT2 protein and function is commonly found in Alzheimer’s Disease (AD) patients. We have
discovered and developed a novel series of small molecules that can increase EAAT2 expression via
a novel translational activation mechanism. These molecules have been proved to be capable of
normalizing glutamate dyshomeostasis and providing significant benefits in two mouse models of AD.
This project is currently at the pre-clinical development stage. However, our original lead compound
was identified with a phenotypic approach. At this point, we still don't know the compound target. The
focus of this study is to identify the target protein of LDN/OSU-215111, which is our pre-clinical
candidate. In Aim 1, we will utilize, in tandem, an affinity probe pull-down approach and a protein
microarray approach to identify putative compound targets. In Aim 2, We will investigate the identified
candidates and determine the target protein that is responsible for LDN/OSU-215111-mediated
EAAT2 induction. We will first validate the interaction of LDN/OSU-215111 with the identified proteins
in vitro. Once the interaction is confirmed, we will investigate if knockdown of the candidate protein
results in loss of LDN/OSU-215111-mediated EAAT2 induction. The goal is to determine the
compound target.

## Key facts

- **NIH application ID:** 9885609
- **Project number:** 1R21AG066059-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** CHIEN-LIANG GLENN LIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,800
- **Award type:** 1
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9885609

## Citation

> US National Institutes of Health, RePORTER application 9885609, Target identification of small molecule LDN/OSU-215111 (1R21AG066059-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9885609. Licensed CC0.

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