. Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor. J Neurosci. 2011 Nov 16;31(46):16507-16. PubMed.

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  1. LY2811376 represents a breakthrough in targeting BACE1, the protease that initiates the amyloid cascade. After 10 years of research, many in the field were beginning to question whether this critical protease could be targeted with a small-molecule inhibitor. While previously presented at international meetings, the data in this article represent the first disclosure in a peer-reviewed journal of an orally available small-molecule inhibitor of BACE, and a critical first step in the development of a BACE inhibitor to test the amyloid hypothesis. While development of LY2811376 has been terminated, Lilly has in clinical development another β-secretase inhibitor which replicates and extends the pharmacodynamic responses observed in humans with LY2811376.