# Discovery of Chemical Probes and Therapeutic Leads, Phase 2

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2023 · $944,312

## Abstract

PROJECT SUMMARY
 The goal of the parental COBRE award, entitled Discovery of Chemical Probes and Therapeutic Leads,
is to develop chemical approaches for probing biology, to discover and apply new chemical biological tools for
the study of disease-associated biological pathways, and to understand the interactions between small
molecules and their biological targets using computational approaches. In this supplement award application,
we propose to develop probes and inhibitors and use these new tools to study the fundamental biochemical
properties of ADAM9, a cell-surface metalloproteinase that is a biomarker and a potential therapeutic target for
multiple human diseases. Aim 1 of this application (led by Dr. Wei) will be focused on developing sensitive and
selective fluorescent peptide substrates for ADAM9, which are currently unavailable. These peptide substrates
are necessary for high-throughput screens to identify ADAM9 inhibitors, and for generating biosensors to
detect endogenous ADAM9 activity in animal and clinical samples as a biomarker. Aim 2 (led by Dr. Schmitz)
will investigate the molecular basis of ADAM9-inhibitor interactions by using an ADAM9 inhibitor that we
recently identified. This information is crucial for guiding future identification and optimization of ADAM9
inhibitors. In Aim 3 (led by Dr. Langhans), we will test the feasibility of identifying new ADAM9 inhibitors by
conducting a medium-throughput screen with a library containing thousands of compounds. Hits identified in
this screen will serve as leads for further optimization to develop potent and selective ADAM9 inhibitors for
research and clinical purposes. The proposed study will leverage the unique and complementary skill set of
each co-project leader: Dr. Wei is an experienced researcher specializing in metalloproteinase biochemistry
and cell biology, Dr. Schmitz is a structural biologist focusing on protease structure-function relationship, and
Dr. Langhans, the acting director of the High-Throughput Screen Core Facility at Nemours Children’s Hospital,
will contribute her expertise in drug screen. The collaboration will be highly synergistic, as extensive
interactions among the three research groups are anticipated for each aim. At the completion of this project,
we expect to submit a multi-PI R01 application using the data generated from this study to continue and
deepen our collaboration. In conclusion, the proposed collaborative research will have a long-term and
transformative impact on understanding the pathology of the related diseases and developing new drugs to
treat these diseases.

## Key facts

- **NIH application ID:** 10853967
- **Project number:** 3P20GM104316-09S2
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** JOSEPH M FOX
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $944,312
- **Award type:** 3
- **Project period:** 2014-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853967

## Citation

> US National Institutes of Health, RePORTER application 10853967, Discovery of Chemical Probes and Therapeutic Leads, Phase 2 (3P20GM104316-09S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10853967. Licensed CC0.

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