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XH1 is a novel bifunctional lipophilic metal chelator developed by researchers at Massachusetts General Hospital and the University of Melbourne for the treatment of Alzheimer's disease. Designed using a 'pharmacophore conjugation' concept, the small molecule contains both an amyloid-binding moiety and a metal-chelating moiety (targeting zinc, iron, and copper) connected by amide bonds. XH1 is engineered to cross the blood-brain barrier and address the dysregulation of cerebral biometals that contributes to amyloid-beta (Aβ) pathology. In preclinical studies, it has demonstrated the ability to reduce zinc-induced Aβ aggregation and specifically attenuate the expression of Amyloid Precursor Protein (APP) in neuroblastoma cells. In transgenic mouse models (PS1/APP), XH1 treatment reduced cerebral Aβ amyloid pathology without significant neurotoxicity.
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