Alzheimer's disease (AD) is a progressive and devastating neurodegenerative disorder, characterized by the presence of β-amyloid (Aβ) peptide plaques, neurofibrillary tangles, and neuroinflammation. Receptor for advanced glycation end products (RAGE) belongs to the immunoglobulin superfamily, which functions as a cell surface acceptor for Aβ peptide. RAGE plays an important role in the Aβ-mediated neuronal damage that closely related to the pathogenesis of AD. In this study, Compound 12 showed good dual-target bioactivities against RAGE and SERT in vitro, good liver microsomal stability, and acceptable pharmacokinetic properties. Pharmacokinetic studies were commissioned by Medicilon.

Reference:

Chao Zhang, et al. Discovery of novel dual RAGE/SERT inhibitors for the potential treatment of the comorbidity of Alzheimer's disease and depression. Eur J Med Chem. 2022 Jun 5;236:114347. doi: 10.1016/j.ejmech.2022.114347.