Discovery and Characterization Small Molecule Modulators of Striatal‐Enriched Protein Tyrosine Phosphatase (STEP) for Alzheimer’s Disease Therapeutics

Description

Jiaqian Wu, Ye Na Han, Nicholas Cosford, and Lutz Tautz hunt for drug-like molecules that remove a brain enzyme tied to Alzheimer disease. The enzyme, called STEP, rises under the influence of amyloid and works against the strengthening of synapses, which the authors link to memory loss. Blocking or reducing it rescued thinking in mouse models, so the target is validated but hard to drug. Writing in twenty twenty-five, the team screened a thousand small fluorine-bearing fragments with magnetic resonance methods to find ones that grip the enzyme, then confirmed the grips with several binding tests.

Strong, selective fragments emerged. From the best binder they built degrader molecules that tag the enzyme for disposal. The degraders cleared the enzyme from human nerve-like cells, and one crossed into the brain and worked in living animals. The authors call them first-in-class tools against early synaptic failure.

Catalog record

Source: https://europepmc.org/articles/PMC11713597