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Computationally Driven Design of Novel BACE-1 Inhibitors for Alzheimer's Disease

Chinn, M. M.; Mateos, D. L.; Riley, M. A.; Siegel, J. B.

2023-11-16 biochemistry
10.1101/2023.11.15.567308 bioRxiv
Show abstract

Alzheimers disease is the most common form of dementia affecting 35 million people globally. One of the major efforts in the development of a treatment for Alzheimers is to reduce the rate of plaque formation, the common hallmark of Alzheimers disease. The protease BACE-1 has been demonstrated to play a role in catalyzing plaque formation and is therefore a major drug target. Here we report potential new drug candidates building upon Verubecestat, developed through computationally driven molecular modeling methods. Both designed molecules have improved docking scores relative to Verubecestat when modeled in the BACE-1 active site, and therefore present potential new leads for more effective therapeutics to combat Alzheimers disease.

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