Bi-functional inhibitors of beta- and gamma-secretase for reducing amyloid-beta in Alzheimer's disease (Hadasit)
There is a strong need for novel selective and safe approaches for the management of Alzheimer's disease.Development of selective bi-functional small molecules aimed to simultaneously inhibit beta- and gamma secretases in order to reduce amyloid-beta (Aβ) while avoiding toxic effects of full enzymatic blocking. We are using a prize winning algorithms for selecting novel bi-functional molecules characterized by improved safety profile and enhanced CNS delivery. The in Silico model was used to pick 50 molecules out of 18 million as top potential bi-functional candidates. Out of those 50 bi-functional candidates only 5 have been purchased and tested in vitro yielding already 2 compounds which reduced Amyloid beta levels in PC12 cells in low micromolar concentrations. The dual inhibition of both beta- and gamma secretases by the selected candidates has yet to be determined.
Selective bi-functional small molecules aimed to simultaneously inhibit beta- and gamma secretases in order to reduce amyloid-beta (Aβ) while avoiding toxic effects of full enzymatic blocking.
Alzheimer's disease
8-2012-223
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