Related Experiment Video
Updated: Jul 15, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Targeting Histone Acetyltransferases EP300/CBP by Novel Proline-Based PROTAC Degraders
Kathrin Tan1, Melina Vogt2, Katerina Schaal2
1Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
ACS Medicinal Chemistry Letters
|July 14, 2026
Summary
Researchers developed a novel PROTAC (proteolysis-targeting chimera) that selectively degrades EP300, a key cancer target. This EP300 degrader showed promise in halting cancer cell growth and inducing cell death.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- EP300 and CBP are homologous enzymes and promising oncology targets.
- Targeting the histone acetyltransferase (HAT) domain of EP300/CBP can lead to selective degradation.
- PROTACs offer a novel therapeutic strategy by hijacking cellular degradation machinery.
Purpose of the Study:
- To design and synthesize novel HAT-targeting PROTACs for EP300/CBP.
- To evaluate the potential of HAT domain engagement for achieving paralog selectivity.
- To assess the anti-cancer effects of selective EP300 degradation.
Main Methods:
- Design and synthesis of proline-based HAT-targeting PROTACs.
- Characterization of novel compounds, including compound 25a.
- Functional studies in REH cells to assess proliferation, cell cycle, and apoptosis.
Main Results:
- Compound 25a demonstrated preferential degradation of EP300 over CBP.
- Selective EP300 degradation by 25a impaired REH cell proliferation.
- Treatment with 25a induced G1 cell cycle arrest and apoptosis in REH cells.
Conclusions:
- HAT domain engagement is a viable strategy for achieving paralog-selective EP300/CBP degradation.
- Compound 25a is a promising lead for developing therapeutics against EP300-dependent cancers.
- Targeted EP300 degradation offers a potential therapeutic avenue for malignancies driven by EP300.
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