# Development of a lead cyclic-PDZ-Enhancer drug for Anxiety and Depression

> **NIH NIH R41** · AINGEAL, LLC · 2020 · $452,622

## Abstract

Major depressive disorder is a debilitating mood disorder that affects ~7% of US adults in their lifetime,
costing the U.S. economy more than $200 billion a year. Drugs that increase monoaminergic signaling
are the mainstay of depression therapy, but have a delayed onset of action and are only effective in
about 50% of affected patients. Aberrant brain-derived neurotrophic factor (BDNF) signaling has been
proposed to underlie the pathophysiology of major depressive disorder and Bipolar disorder.
We have developed a novel family of cyclic peptidomimetic compounds that potentiate the BDNF
pathways to produce rapid (within hours) antidepressant effects. Here, we propose a Phase I proof-of-
concept and feasibility study for the use of our patented new drug, CN2097, for treating depression.
There are three major goals that focus on preclinical efficacy. Aim 1 will test the stability of CN2097
analogues and evaluate toxicity. Aim 2 will evaluate the rapid and long-term effects of treatment
with CN2097 in mitigating depressive behaviors using two extensively validated models: Chronic
mild stress (CMS) and Chronic social defeat stress (CSDS). Aim 3 will examine the ability of
CN2097 to correct impairments in the cellular mechanisms of depression that include signaling,
neuronal atrophy and synaptic plasticity.

## Key facts

- **NIH application ID:** 10015345
- **Project number:** 5R41MH118747-02
- **Recipient organization:** AINGEAL, LLC
- **Principal Investigator:** JOHN MARSHALL
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $452,622
- **Award type:** 5
- **Project period:** 2019-09-10 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015345

## Citation

> US National Institutes of Health, RePORTER application 10015345, Development of a lead cyclic-PDZ-Enhancer drug for Anxiety and Depression (5R41MH118747-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10015345. Licensed CC0.

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