1. Academic Validation
  2. Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer's Disease

Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer's Disease

  • ChemMedChem. 2015 Sep;10(9):1463-6. doi: 10.1002/cmdc.201500216.
Arun K Ghosh 1 2 Jordan Tang 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Purdue University, West Lafayette, IN 47907 (USA). [email protected].
  • 2 Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 (USA). [email protected].
  • 3 Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104 (USA).
Abstract

β-Secretase continues to be an attractive drug discovery target for the therapeutic intervention of Alzheimer's disease (AD). This Enzyme plays a critical role in the production of neurotoxic β-amyloid (Aβ) Peptides in the brain. Over the years, extensive research efforts have led to the development of many promising classes of inhibitors against this protease. Many small-molecule, peptidomimetic, and nonpeptide β-secretase inhibitors have now overcome the key challenging development hurdles such as selectivity and brain penetration. A number of inhibitors have also shown further promise in reducing brain Aβ and rescuing cognitive decline in animal models. Recently, several β-secretase inhibitors have entered into preclinical and phase I studies, and at least one of these inhibitors has advanced to phase II/III human trials. The outlook on β-secretase inhibitor drugs for the treatment of AD patients is discussed herein.

Keywords

Alzheimer’s disease; BACE1; BACE2; cathepsin D; memapsin 2; protease inhibitors; β-secretase.

Figures
Products