# Targeting chemoresistant prostate cancer with novel EED inhibitors

> **NIH NIH R01** · CLARK ATLANTA UNIVERSITY · 2024 · $104,961

## Abstract

Docetaxel is the first-line chemotherapy for metastatic castration-resistant prostate cancer (PCa), the major
cause of PCa mortality. Unfortunately, in most cases PCa develops docetaxel resistance and continues to
progress, which has no cure. Our recent studies (Theranostics, 2021, May 8; 11: 6873-6890) have provided
strong evidence demonstrating that chemoresistant PCa cells rely on an active EED-EZH2-Stat3-SKP2-
ABCB1/survivin signaling to survive and evade standard chemotherapy. In this R01 project, we hypothesize
that targeting EED-EZH2 interaction with novel EED inhibitors is effective to overcome chemoresistance and
eliminate lethal PCa cells. In Aim 1, we will conduct rational design and chemical optimization of novel EED
inhibitors. A total of 200 new chemical entities will be designed and synthesized. In Aim 2, We will validate the
mechanism of action of potential leads in chemoresistant PCa cells. We will identify the in vitro and in vivo
activities of new EED inhibitors against chemoresistant PCa in multiple, heterogenous preclinical models of
chemoresistant PCa. In Aim 3, we will conduct Good Laboratory Practice (GLP) and non-GLP studies to
evaluate the drug-like properties of lead compounds, including pharmacokinetics, absorption, distribution,
metabolism, and excretion (ADME), single- and repeat-dose toxicity and safety pharmacology. With successful
accomplishment of this project, we expect to identify 1~2 patentable lead compounds and advance them into
further preclinical and clinical development. The overarching goal is to translate our basic research into an
effective and safe treatment for lethal PCa, therefore benefiting patients and improving clinical outcomes.

## Key facts

- **NIH application ID:** 10832584
- **Project number:** 5R01CA256058-03
- **Recipient organization:** CLARK ATLANTA UNIVERSITY
- **Principal Investigator:** DAQING WU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $104,961
- **Award type:** 5
- **Project period:** 2022-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832584

## Citation

> US National Institutes of Health, RePORTER application 10832584, Targeting chemoresistant prostate cancer with novel EED inhibitors (5R01CA256058-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10832584. Licensed CC0.

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