# Evaluation of Trk Probes in Models for Dry Eye Disease

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2020 · $100,948

## Abstract

Evaluation Of Trk Probes In Models For Dry Eye Disease
A. Project Summary
In previous work, the PI designed small molecules that resemble turn regions in nerve growth factor
(NGF) and in neurotrophin-3 (NT-3), for two reasons. First, β-turn regions in the neurotrophins seem
to be hot-spots for their interactions with the tropomyosin receptor kinase (Trk). Second, whereas
neurotrophins activate both the Trk receptors and another receptor called p75, the small molecules
should only activate the Trk receptors; this is important because activation of p75 has been
associated with induction of apoptosis. In the event, several partial agonists were found, and one of
them progress to phase 3 clinical trials (Mimetogen) for treatment of dry eye disease, and its fate as a
pharmaceutical has yet to be decided. Most of the compounds prepared in that study, however, were
not tested for applications in dry eye disease (they were just screened for properties as Trk ligands),
and none of them were designed or tested for binding to TrkB (selective receptor for brain derived
neurotrophic factor, BDNF). The central hypotheses of this proposal are that: (i) re-synthesis and
testing of some of the original hit NGF and NT3 binding-compounds may afford other leads for
treatment of dry eye disease; (ii) design principles similar to those used before could be enacted to
obtain small molecule ligands that bind TrkB; and, (iii) side-by-side comparison of TrkA, B, and C
probes in models for dry eye disease (cellular and in vivo) will reveal the relative impact of these
compounds, and, by inference, the relative importance of stimulating those receptors in treatment of
dry eye disease.

## Key facts

- **NIH application ID:** 10073894
- **Project number:** 3R01EY029695-02S1
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** KEVIN BURGESS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $100,948
- **Award type:** 3
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073894

## Citation

> US National Institutes of Health, RePORTER application 10073894, Evaluation of Trk Probes in Models for Dry Eye Disease (3R01EY029695-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073894. Licensed CC0.

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