# Developing a cell-based high throughput screening for USP15 deubiquitinase inhibitor discovery

> **NIH NIH R21** · UNIVERSITY OF DELAWARE · 2021 · $434,686

## Abstract

Developing a cell-based high throughput screening for USP15 deubiquitinase inhibitor discovery
 The goal of this project is to develop a ubiquitin probe-based AlphaLISA deubiquitinase HTS assay that
enables cell-based and high throughput screening for human deubiquitinase USP15. It is now clear that the
human ubiquitin system is fundamentally important to the normal cellular and organismal functions.
Deubiquitinases or DUBs as an important class of enzyme have been associated with neurological disorders,
particularly Parkinson’s disease (PD). Many disease-relevant and potentially druggable deubiquitinases are
currently inaccessible to HTS-based inhibitor discovery due to the difficulty in their purification as homogeneous
and active recombinant proteins in quantity large enough for HTS campaign. In this proposal, we aim at
developing a cell-based AlphaLISA deubiquitinase assay for high throughput screening against USP15 and other
DUBs, and setting the ground work for identifying and developing USP15 inhibitors with a mitophagy-promoting
effect and the potential being developed into PD therapeutics.

## Key facts

- **NIH application ID:** 10287750
- **Project number:** 1R21NS123322-01
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Zhihao Zhuang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $434,686
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287750

## Citation

> US National Institutes of Health, RePORTER application 10287750, Developing a cell-based high throughput screening for USP15 deubiquitinase inhibitor discovery (1R21NS123322-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10287750. Licensed CC0.

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