Compositions and methods for the inhibition of dishevelled proteins

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United States of America Patent

APP PUB NO 20080119402A1
SERIAL NO

11097518

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ATTORNEY / AGENT: (SPONSORED)

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The Wnt signaling pathways are involved in embryo development as well as in tumorigenesis. Dishevelled (Dvl) tranduces Wnt signals from the receptor Frizzled (Fz) to downstream components in canonical and non-canonical Wnt signaling pathways, and the Dvl PDZ domain plays an essential role in both pathways, and the Dvl PDZ domain binds directly to Fz receptors. In the present invention using NMR-assisted virtual ligand screening, several compounds were identified and were found to bind to the Dvl PDZ domain. Molecular dynamics simulation was used to analyze the binding between the PDZ domain and these compounds in detail. These compounds provide a basis for rational design of high-affinity inhibitors of the PDZ domain, which can block Wnt signaling by interrupting the Fz-Dvl interaction.

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Inventor(s)

Inventor Name Address # of filed Patents Total Citations
Shan, Jufang Memphis, US 2 63
Wu, Dianqing Cheshire, US 16 83
Zheng, Jie Memphis, US 190 1175

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