In vitro activity: Atabecestat (formerly known as JNJ-54861911) is a novel potent, oral, and brain-penetrant inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which is an enzyme that is up-regulated in Alzheimer’s disease. β-Secretase enzyme (BACE) inhibition has been proposed as a priority treatment mechanism for Alzheimer's disease (AD), but treatment initiation may need to be very early. JNJ-54861911 was found to inhibit BACE1 with approximately 2,600 nM affinity to 1 nM affinity. JNJ-54861911 was well-tolerated, adverse events were uncommon and unrelated to JNJ-54861911. JNJ-54861911 showed dose-proportional CSF and plasma pharmacokinetic profiles.

Kinase Assay: JNJ-54861911 inhibited BACE1 with IC50 of 2,600 nM to 1 nM.