Aβ42-IN-1, compound 1v, is a novel, potent and orally active γ-secretase modulator (GSM). Aβ42-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ42-IN-1 shows a sustained pharmacokinetic profile.

Aβ42-IN-1, administered orally at a dosage of 30 mg/kg, exhibits a favorable pharmacokinetic profile in mice and significantly decreases Aβ42 levels in both the brain and plasma by 36% and 66%, respectively. This reduction indicates its efficacy in lowering amyloid-beta peptides, although the brain/plasma ratio of the compound 1v is marginally less than that of 1a [1]. This study was conducted on 8-week-old male ddY mice, highlighting the compound's potential benefits in amyloid-beta related studies.