Beta-secretase

The β-secretase (BACE) is an enzyme in the CNS critically involved in the pathogenesis of Alzheimer’s disease. This enzyme is responsible for the cleavage of Amyloid Precursor Protein and the associated creation of beta-amyloid Aβ 40-42, a neurotoxic peptide believed to be causally linked to Alzheimer’s disease.

We believe that by creating small molecule inhibitors of BACE activity we create drug candidates that have the potential to fundamentally alter the course of Alzheimer’s disease. This would represent a significant advance over current therapies which provide only symptomatic relief without affecting the onset or progression of disease.

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OM99-2 (Ghosh et al., JACS, 2000)

 

Drs. Jordan Tang and Arun Ghosh, two of the scientific founders of CoMentis, are pioneers in the field of aspartic proteases. Since publication of the first beta-secretase inhibitor in 2000, Dr. Tang has led the characterization of this enzyme’s role in Alzheimer’s disease and Dr. Ghosh has led the construction of drug candidates to inhibit its activity. The action of this enzyme on the amyloid precursor protein leads to the formation of plaques in the brain and is implicated in the development of Alzheimer’s disease. Inhibition of beta-secretase reduces amyloid beta production and could slow the progression of Alzheimer’s disease. CTS-21166 is the first of several highly selective, potent and orally active beta-secretase inhibitors being developed by CoMentis that show excellent efficacy in preclinical models of Alzheimer’s disease.