JNJ-40418677

JNJ-40418677 is a modulator of γ-secretase.¹ It reduces the levels of amyloid-β (1-42) (Aβ42; Item No. 20574) in a cell-free γ-secretase modulation assay. It also reduces the secretion of Aβ42, but not total Aβ, in SK-N-BE(2) human neuroblastoma cells expressing amyloid precursor protein (APP; mean IC₅₀ = 200 nM) and in primary rat cortical neurons (mean IC₅₀ = 185 nM). JNJ-40418677 (100 and 300 mg/kg) reduces the level of Aβ42 in wild-type mouse brain. It decreases brain levels of Aβ42, Aβ40, and Aβ38 in the deposited fraction, and Aβ42 and Aβ40 in the soluble fraction, in the Tg2576 mouse model of Alzheimer’s disease when administered at doses of 60 and 120 mg/kg per day in the diet for seven months. It also reduces increases in the number of amyloid plaques in Tg2576 mouse brain compared to vehicle control animals.

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1. Van Broeck, B., Chen, J.-M., Tréton, G., et al. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer’s disease. Br. J. Pharmacol. 163(2), 375-389 (2011).