TPT-260 (TPU260), a thiophene thiourea derivative, is a retromer complex stabilizer against thermal denaturation ( K d = ~5 µM). TPT-260 increases the levels of retromer proteins, shifts amyloid-precursor protein (APP) away from the endosome, and decreases the pathogenic processing of APP. TPT-260 inhibits TLR4 upregulation, IKKβ phosphorylation, NF-κB p65 nuclear translocation, and NLRP3 inflammasome formation. TPT-260 improves retromer-mediated cargo trafficking, reduces brain infarct area, and decreases amyloid plaque deposition. TPT-260 exhibits minimal cytotoxicity to primary microglia at tested concentrations. TPT-260 can be used for the research of inflammatory bowel disease, ischemic stroke and Alzheimer's disease.
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