JNJ-40418677，≥98% (HPLC)

JNJ-40418677 is a γ-secretase modulator that selectively blocks γ-site cleavage of the APP without affecting processing of Notch. In human neuroblastoma cells and rat primary neuronal cultures, JNJ-40418677 blocked secretion of Aβb42 (IC₅₀ = 20 nM), with no affects on total Ab concentration, Notch signaling or COX activity. In vivo experiments showed that JNJ-40418677 dose dependently inhibited Aβ42 accumulation in the brain while promoting an increase in Aβ38.