CONTEXT

Down’s Syndrome (DS) is the most common genetic disorder with a frequency of 1 in 700 live births worldwide, and it is associated with an increased risk of Alzheimer’s disease. DYRK1A is considered a pathogenic factor in DS and has been implicated in the abnormal hyperphosphorylation of tau protein in Alzheimer’s disease brain.

TECHNICAL DESCRIPTION

The inventors have designed new azaindole-based DYRK1A inhibitors that demonstrate potent activity against DYRK1A and high affinity for the ATP-binding site. In vitro evaluation and computer-guided molecular design were used to select the appropriate candidates. No cytotoxicity has been detected, and primary data obtained on wild-type and DS model mice are very promising. For example, recent studies show that 2 weeks treatment with the new DYRK1A inhibitor was sufficient to improve the performances of DS mice model (Ts65Dn) in the Morris Water Maze.

This work is financially supported by the programme “Emergence of high potential products or services” of the Agence Nationale pour la Recherche.

PUBLICATIONS

Development of DANDYs, new 3,5-diaryl-7-azaindoles demonstrating potent DYRK1A kinase inhibitory activity.
Gourdain S, Dairou J, Denhez C, Bui LC, Rodrigues-Lima F, Janel N, Delabar JM, Cariou K, Dodd RH.
J Med Chem. 2013 Dec 12;56(23):9569-85

For further information, please contact us (Ref 05433-01)