Aβ/tau aggregation-IN-1 is a potent inhibitor of Aβ 1-42 β-sheet formation and tau aggregation, exhibiting K D values of 160 μM and 337 μM with Aβ 1-42 and tau, respectively. Additionally, Aβ/tau aggregation-IN-1 efficiently penetrates the blood-brain barrier.

Tau:337 μM (Kd), β-Amyloid (1–42):160 μM (Kd)

Aβ/tau aggregation-IN-1 (1 μM; 24 hours; HEK-293 T cells) significantly reduces tau aggregation foci. By incorporating N-methylation on the quinolone ring, the compound inhibits Aβ 1-42 aggregation by 84.7%–99.5% and tau by 71.2%–101.8%, prevents self-induced Aβ 1-42 aggregation by blocking β-sheet formation, and shows notable affinity for Aβ 1-42 and tau, with K_D values of 160 μM and 337 μM, respectively, mediated via noncovalent bonds. Immunofluorescence assays in HEK-293 T cells confirm a significant reduction in tau aggregation foci.