# Core A: Analytical and Medicinal Chemistry Core

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $273,700

## Abstract

Project Summary – Analytical and Medicinal Chemistry (AMC) Core – Core A
The overall goal of the new UC Davis CounterACT Center of Excellence is to identify and advance novel
therapeutic strategies that, when administered as an adjunct to in-field standard-of-care (SOC) for acute
organophosphate (OP) intoxication, will mitigate the onset and/or severity of long-term, adverse neurological
consequences. Current medical countermeasures, which include the muscarinic receptor antagonist, atropine,
combined with an oxime, to reactivate acetylcholinesterase and a benzodiazepine to terminate status epilepticus,
do not sufficiently protect against the development of spontaneous recurrent seizures (SRS) and cognitive
deficits unless administered in the first 15-min after exposure. Therefore, there exists an urgent need to identify
novel therapeutic strategies that can be deployed at delayed times post-exposure to mitigate the chronic,
adverse neurological sequelae of acute OP intoxication. There is also a critical need to identify quantifiable and
predictive biomarkers that are suitable for evaluating potential therapeutics and that allow prediction of which
patients are at increased risk of developing persistent seizure disorders and cognitive dysfunction and would
most benefit from post-exposure treatment.
The Analytical and Medicinal Chemistry Core (Core A) will function as an integral component of the Center by
supporting and collaborating with all three Projects and the Neuroimaging Core. In general support of the entire
Center, Core A will perform quality control and confirm the identity and purity of all commercially obtained key
chemical resources and the threat agent diisopropylfluorophosphate (DFP). If necessary, compounds will be
purified in-house before release to the Projects. Core A will further support the Projects by developing liquid
chromatography–mass spectrometry (LC/MS) methods for the detection of antiseizure drugs, anti-
inflammatories and neuroprotectants and their metabolites in plasma and tissues, and generate pharmacokinetic
data to inform dose selection and demonstrate target engagement. Core A will use its medicinal chemistry
expertise to synthesize small molecule probes and potential novel therapeutics as required by the Projects.
Additionally, Core A will closely work with the Projects on the identification and quantification of biomarkers for
seizure activity, neuroinflammation and changes in blood-brain-barrier permeability and their amelioration by
potential therapeutics. Oversight and management of the Core will be provided by Core Lead, Heike Wulff, PhD,
Professor of Pharmacology at UC Davis with broad expertise in pharmacology and medicinal chemistry; and
Core Co-Lead, Jun Yang, PhD, Research Scientist at UC Davis, with extensive expertise in mass spectrometry
and both global and targeted metabolomics, particularly lipid mediators. By providing analytical and medicinal
chemistry expertise, and dedicated services of prob...

## Key facts

- **NIH application ID:** 10911232
- **Project number:** 5U54NS127758-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** HEIKE WULFF
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $273,700
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911232

## Citation

> US National Institutes of Health, RePORTER application 10911232, Core A: Analytical and Medicinal Chemistry Core (5U54NS127758-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10911232. Licensed CC0.

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