iododiflunisal and tafamidis

Transthyretin (TTR) is a homotetrameric protein involved in human amyloidosis, including familial amyloid polyneuropathy (FAP). Discovering small-molecule stabilizers of the TTR tetramer is a therapeutic strategy for these diseases. Tafamidis, the only approved drug for FAP treatment, is not effective for all patients. Herein, we discovered that benzbromarone (BBM), a uricosuric drug, is an effective TTR stabilizer and inhibitor against TTR amyloid fibril formation. BBM rendered TTR more resistant to urea denaturation, similarly to iododiflunisal (IDIF), a very potent TTR stabilizer. BBM competes with thyroxine for binding in the TTR central channel, with an IC

Topics: Amyloid; Benzbromarone; Benzoxazoles; Binding Sites; Binding, Competitive; Crystallography, X-Ray; Diflunisal; Drug Repositioning; Gene Expression; Humans; Hydrogen Bonding; Kinetics; Molecular Docking Simulation; Neuroprotective Agents; Prealbumin; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Multimerization; Protein Stability; Recombinant Proteins; Thermodynamics; Thyroxine; Tolcapone