Proteolysis-targeting chimeras (PROTACs) represent a promising modality for targeted protein degradation, yet their structural complexity complicates systematic design and analysis. Bellerophon is a new computational tool that automatically decomposes PROTACs into their warhead, linker, and E3 ligase ligand directly from molecular structure. By enabling automated and standardized decomposition of degraders, the tool facilitates drug design at different levels: Bellerophon demonstrated versatility for moiety replacement (ARV-110), large-scale annotation (PROTAC-DB) and linker analysis (IRAK4 data set). The tool is freely available through a user-friendly web interface, with open-source code to encourage transparency and collaborative development in chemical biology and medicinal chemistry.
Apprato et al. (2026) studied this question.