Research ArticleAlzheimer’s Disease

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients

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Science Translational Medicine  02 Nov 2016:
Vol. 8, Issue 363, pp. 363ra150
DOI: 10.1126/scitranslmed.aad9704

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Getting to first BACE

The discovery of BACE1 inhibitors that reduce β-amyloid peptides in Alzheimer’s disease (AD) patients has been an encouraging development in the quest for a disease-modifying therapy. Kennedy and colleagues now report the discovery of verubecestat, a structurally unique, orally bioavailable small molecule that potently inhibits brain BACE1 activity resulting in a reduction in Aβ peptides in the cerebrospinal fluid of animals, healthy volunteers, and AD patients. No dose-limiting toxicities were observed in chronic animal toxicology studies or in phase 1 human studies, thus reducing safety concerns raised by previous reports of BACE inhibitors and BACE1 knockout mice.