Control of β-secretase activity and development of its inhibitors

Tatsuto Fukushima

Neurology Tsukuba Research Department, Discovery, Medicine creation, Neurology Business Group, Eizai Co., Ltd.

Cleavage of amyloid precursor protein by β-secretase (BACE1) is the first step in amyloid β (Aβ) production and inhibition of β-secretase is thought to be the prime target for blocking the pathogenic amyloid cascade leading to Alzheimer's disease (AD). After discovery of BACE1 as β-secretase, the challenges of creating brain-active BACE1 inhibitors by overcoming the limited brain efficacy due to poor bioavailability and liability of p-pg transport substrate have been continued. Currently some BACE1 inhibitors are under clinical development in AD. It is hoped that BACE1 inhibitors stop disease progression in AD by sufficient inhibition of Aβ production in brain.

Address correspondence to Ms. Tatsuto Fukushima, Neurology Tsukuba Research Department, Discovery, Medicine creation, Neurology Business Group, Eizai Co., Ltd.(5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan)