1. Fragment-based discovery of nonpeptidic BACE-1 inhibitors using tethering
- Author
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Wenjin Yang, Fucini, Raymond V., Fahr, Bruce T., Randal, Mike, Lind, Kenneth E., Lam, Melissa B., Wanli Lu, Yafan Lu, Cary, Douglas R., Romanowski, Michael J., Colussi, Dennis, Pietrak, Beth, Allison, Timothy J., Munshi, Sanjeev K., Penny, David M., Pham, Phuongly, Jian Sun, Thomas, Anila E., Wilkinson, Jennifer M., Jacobs, Jeffrey W., McDowell, Robert S., and Ballinger, Marcus D.
- Subjects
Glycoproteins -- Structure ,Glycoproteins -- Chemical properties ,Alzheimer's disease -- Research ,Enzyme inhibitors -- Research ,Ligand binding (Biochemistry) -- Analysis ,Biological sciences ,Chemistry - Abstract
Tethering technology to discover small molecule fragment ligands that bind to the enzyme active site was utilized to survey BACE-1 ([beta]-site amyloid precursor protein cleaving enzyme), a prominent target in Alzheimer's disease drug. The study identified aminobenzylpiperidine (ABP) ligands as a new type of nonpeptidic BACE-1 inhibitor motif that might serve as a starting point for the development of BACE-1-directed Alzheimer's disease therapeutics.
- Published
- 2009