🙌 Huge thanks to all authors, and to Phospho Biomedical Animation for the stunning cover!

📚 Full issue: pubs.acs.org/toc/jacsat/1...
📄 Paper: pubs.acs.org/doi/10.1021/...

@radford-lab.bsky.social @naranson.bsky.social

#amyloid #chemsky #diabetes #proteinaggregation

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🔎 This reveals a possible new strategy to treat diseases involving amyloid formation – kinetic steering to divert aggregation down a less toxic route.

⚡ But it also suggests that formation conditions can kinetically, not just thermodynamically, determine fibril polymorphism in disease.

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But then we had a surprise – cana and a related inhibitor also profoundly change the final structure of amyloid fibrils.

This suggests that early events in amyloid formation are crucial for determining the subsequent structures of fibril polymorphs.

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Cana is already a type-2 diabetes drug with an unrelated mode of action, and may currently be given too late to affect islet amyloid formation.

But could earlier treatment with cana (or doxa) help to treat type-2 diabetes? We think these drugs are promising leads for future work.

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This started as a drug repurposing study, asking whether existing drugs have untapped potential to treat IAPP amyloid formation, involved in type-2 diabetes.

Our repurposing screen identified two hits – canagliflozin (cana) and doxazosin (doxa) - which target early steps in aggregation.

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