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Bellerophon: An Automated Tool for PROTAC Decomposition.

Giulia Apprato¹, Matteo Bertola², Amelia Locatelli¹

¹Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino 10126, Italy.

ACS Medicinal Chemistry Letters

|May 20, 2026

Summary

This summary is machine-generated.

Bellerophon is a new computational tool that simplifies the analysis of proteolysis-targeting chimeras (PROTACs). This tool aids in drug design by automatically decomposing PROTACs, facilitating research in targeted protein degradation.

Keywords:

PROTAC TPD decomposition tool drug discovery

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Area of Science:

Medicinal Chemistry
Chemical Biology
Computational Chemistry

Background:

Proteolysis-targeting chimeras (PROTACs) are a novel therapeutic modality for targeted protein degradation.
The structural complexity of PROTACs presents challenges for systematic design and analysis.
Efficient tools are needed to streamline PROTAC research and development.

Purpose of the Study:

To introduce Bellerophon, a computational tool for automated PROTAC decomposition.
To facilitate systematic design and analysis of PROTACs.
To support drug discovery efforts in targeted protein degradation.

Main Methods:

Bellerophon automatically decomposes PROTAC structures into their core components: warhead, linker, and E3 ligase ligand.
The tool analyzes molecular structures to identify and separate these functional moieties.
A user-friendly web interface and open-source code are provided.

Main Results:

Bellerophon demonstrated versatility in moiety replacement, exemplified by the ARV-110 dataset.
The tool enabled large-scale annotation of the PROTAC-DB database.
Bellerophon facilitated detailed linker analysis using an IRAK4 dataset.

Conclusions:

Bellerophon offers automated and standardized decomposition of PROTACs.
The tool supports various levels of drug design, including moiety replacement and database annotation.
Bellerophon promotes transparency and collaboration in chemical biology and medicinal chemistry research.