Journal of medicinal chemistry

Improving p62-Targeting AUTOTACs to Better Break Down Cancer-Related Proteins EGFR and VEGFR2 and Fight Tumors

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Abstract

Two potent AUTOTAC degraders, 6d and 11bg, selectively degrade EGFR and VEGFR2.

  • AUTOTAC degraders target receptor tyrosine kinases (RTKs), which are important in cancer therapy.
  • These degraders work through p62 recruitment and activate the autophagy-lysosome pathway without involving the ubiquitin-proteasome system.
  • Both 6d and 11bg showed strong effects in reducing cancer cell growth, promoting cell death, and inhibiting migration in laboratory settings.
  • 6d also demonstrated significant tumor-fighting effects in live models, with good tolerability observed.

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