Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor

• Published in: Journal of medicinal chemistry Vol. 64; no. 12; pp. 8076 - 8100
• Main Authors: McKinzie, David L, Winneroski, Leonard L, Green, Steven J, Hembre, Erik J, Erickson, Jon A, Willis, Brian A, Monk, Scott A, Aluise, Christopher D, Baker, Thomas K, Lopez, Jose E, Hendle, Jörg, Beck, James P, Brier, Richard A, Boggs, Leonard N, Borders, Anthony R, Cocke, Patrick J, Garcia-Losada, Pablo, Lowe, Stephen L, Mathes, Brian M, May, Patrick C, Porter, Warren J, Stout, Stephanie L, Timm, David E, Watson, Brian M, Yang, Zhixiang, Mergott, Dustin J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.06.2021; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; BETA-SECRETASE; IN-VITRO; ALZHEIMERS-DISEASE; MUTATION; LYSOSOMAL STORAGE; OPTIMIZATION; MICE; AMYLOID PRECURSOR PROTEIN; CLEAVAGE; CATHEPSIN-D DEFICIENCY

The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer’s disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before developme...