# Discovery of PDE2A inhibitors to treat memory deficits in mild cognitive impairment and Alzheimer's disease

> **NIH NIH R43** · FD NEUROTECHNOLOGIES CONSULTING & SERVICES, INC. · 2021 · $499,784

## Abstract

Abstract
Despite the fact that more than 50% of early stage of Alzheimer’s disease (AD) patients with mild cognitive
impairment (MCI) will progress to dementia within 5 years, current therapies provide minimal symptomatic
relief, without curing or halting disease progression. Phosphodiesterase-2A (PDE2A), the most prevalent of
PDEs expressed in the cortex, hippocampus and amygdala, regions involved in cognitive impairment, has
emerged as a promising target for the treatment of mild cognitive impairment without side effects. Despite
promising preclinical data showing that some inhibitors of PDE2A inhibitors, such as Bay 60-7550 and ND
7001, enhance memory in animal models of AD, clinical studies have not advanced, due in part, to the low
selectivity, poor metabolic stability and brain penetrance of available compounds. The broad, long-term goal of
this project is to discover and develop novel inhibitors of PDE2A for the treatment of MCI. To streamline the
exciting project toward a clinical candidate, we have assembled a team with expertise in medicinal chemistry
and drug discovery and PDE-related pharmacology and pharmacokinetics. The complementary collaboration
among FD Neurotechnologies (Dr. Fu Du), University at Buffalo (Drs. Ying Xu and James M. O’Donnell), and
University of Arizona (Dr. Wei Wang) will synergize the effort by utilizing state-of-the-art drug discovery tools
and techniques to discover and optimize novel and drug-like inhibitors of PDE2A and to evaluate their
pharmacological effects in cell and animal models.

## Key facts

- **NIH application ID:** 10255641
- **Project number:** 1R43AG071045-01A1
- **Recipient organization:** FD NEUROTECHNOLOGIES CONSULTING & SERVICES, INC.
- **Principal Investigator:** Fu Du
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,784
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10255641

## Citation

> US National Institutes of Health, RePORTER application 10255641, Discovery of PDE2A inhibitors to treat memory deficits in mild cognitive impairment and Alzheimer's disease (1R43AG071045-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10255641. Licensed CC0.

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