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Condensate screening identifies YM155 as β-catenin condensate inhibitor in colorectal cancer

Manzato, C.; Sirati, N.; Knol, B. A.; Kuiken, H. J.; Morris, B.; Fleming, C.; Beijersbergen, R. L.; Schuijers, J.

2025-01-15 molecular biology
10.1101/2025.01.13.632724 bioRxiv
Show abstract

{beta}-catenin is a transcriptional cofactor crucial in forming biomolecular condensates that drive WNT target gene transcription. Its pathological accumulation in the nucleus is a critical step in WNT-driven cancers, such as colorectal cancer. Disrupting {beta}-catenin condensates is a promising cancer treatment strategy, but no clinical applications currently exist. In this study, we developed a Nanobody Enabled Condensate Observation (NECO) screening platform to identify small molecules that modulate {beta}-catenin condensates. The platform revealed compounds that either enhanced or reduced {beta}-catenin transcriptional condensates. Among them, YM155 (sepantronium bromide) was identified as an inhibitor, disrupting essential weak interactions for condensate formation. This disruption effectively inhibits the proliferation of WNT-driven colorectal cancer organoids. These findings show that the NECO platform can identify small molecules that target {beta}-catenin condensates and suggest YM155 as a potential anti-cancer agent for colorectal cancer.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.