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Small Molecule Blocks RAGE–DIAPH1 Pathway, Reduces Diabetic Tissue Damage in Mice

Peer-reviewed findings highlight a potential route to treat complications by targeting inflammation rather than blood sugar.

Overview

  • The candidate, RAGE406R, prevents DIAPH1 from binding to the RAGE receptor, interrupting an intracellular signaling cascade linked to chronic inflammation.
  • In human cell assays from people with type 1 diabetes, the compound lowered the proinflammatory chemokine CCL2.
  • In diabetic mouse models, topical treatment accelerated wound closure and reduced organ injury associated with heart and kidney damage.
  • Researchers refined RAGE406R after an earlier lead failed a genotoxicity test, removing the structural motif that raised DNA safety concerns.
  • The study appears as a Cell Chemical Biology cover article, with authors disclosing related patents and stating plans to advance toward clinical testing.