# Structure-based drug discovery for Dopamine D2 Receptor Selective Ligands

> **NIH NIH R44** · CONFOMETRX, INC. · 2021 · $738,119

## Abstract

Summary
The neurotransmitter dopamine (DA) controls many central nervous system
functions through three major pathways in the brain, the tuberoinfundibular, the
nigrostriatal and the mesocorticolimic (mesocortical and mesolimbic). Each is
associated with different processes, and dysfunction can lead to varying
diseases and disorders of the central nervous system (CNS). There are five
known DA receptors, D2 (D2R) is one of the most abundant DA receptors in the
brain, and is thus an important pharmacological target for many CNS diseases.
Most of the clinically efficacious antipsychotics used for the treatment of
schizophrenia and Parkinson's disease, which are associated with the
mesocorticolimbic and nigrostriatal pathways, are D2R agonists or antagonists.
However, new drugs with improved efficacy and side-effect profiles are needed
for these relatively prevalent diseases. In addition, several drugs abused by
humans affect DA neurotransmission in the mesolimbic pathway, due to their
effects on reward-related behaviors. Therefore D2R is also a focus for the
discovery of pharmacological treatments for substance abuse of a certain class
of drugs and addiction disorders for which there are none currently available. The
goal of this proposal is to discover novel D2R selective small molecule ligands
that can be developed for the treatment of disorders of the CNS. Utilizing a
combination of D2R three-dimensional structures, including the active-state
structure obtained during our Phase I studies, virtual screening and DNA-
encoded library screening, we will identify and develop novel lead compounds.
These D2R targeted compounds will be optimized and undergo pre-clinical
studies at which point we will seek commercial collaboration with a large
pharmaceutical company.
This proposal is in response to the Funding Opportunity Announcement PA-18-
574, “PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small
Business Innovation Research Grant Applications (Parent SBIR [R43/R44]
Clinical Trial Not Allowed)”.

## Key facts

- **NIH application ID:** 10212202
- **Project number:** 5R44MH115875-04
- **Recipient organization:** CONFOMETRX, INC.
- **Principal Investigator:** Victoria Ahn
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $738,119
- **Award type:** 5
- **Project period:** 2017-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212202

## Citation

> US National Institutes of Health, RePORTER application 10212202, Structure-based drug discovery for Dopamine D2 Receptor Selective Ligands (5R44MH115875-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212202. Licensed CC0.

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