Proteomics maps and reduces off-target toxicity of experimental AR degraders
Academic source · Nature Chemical Biology
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Site published: 2026-11-03 · Updated: 2026-11-03
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What changed
A Nature Chemical Biology study used high-throughput proteomics and machine learning to investigate toxicity in experimental androgen receptor degraders. Researchers linked off-target effects to mitochondrial complex I inhibition and identified small linker changes that reduced hepatotoxicity signals. Optimized compounds retained target degradation and showed improved activity in prostate cancer xenografts, providing preclinical evidence for a safer design workflow.
Why it may matter
The findings make linker design and proteome-wide profiling practical priorities for candidate optimization, with human safety implications still requiring clinical confirmation.
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