Inhibition of fgf signaling

A - Human Necessities – 61 – K

Patent

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Details

A61K 38/46 (2006.01) A61P 35/00 (2006.01) C07K 14/50 (2006.01) C12N 5/02 (2006.01) C12N 9/16 (2006.01)

Patent

CA 2555417

Methods and compositions for inhibiting FGF signaling are described. Methods of the invention include contacting an FGF-responsive cell with exogenous heparan sulfate 6-O endosulfatase (Sulf1) in an amount effective to modify endogenous heparan sulfate, thereby inhibiting FGF signaling. Methods of the invention also include contacting an FGF-responsive cell with an exogenous Sulf1-modified compound, the exogenous Sulf1-modified compound being characterized by the ability to reduce binding of FGF2 or FGF4 to FGFR1. Compositions comprising exogenous Sulf1-modified compounds are also provided for use in conjunction with methods of the present invention.

L'invention concerne des méthodes et des compositions qui permettent d'inhiber la signalisation du FGF (facteur de croissance des fibroblastes). Ces méthodes consistent à mettre une cellule réagissant au FGF en contact avec une endosulfatase de héparane sulfate 6-O (Sulf1) exogène à un taux efficace pour modifier le héparane sulfate endogène, inhibant ainsi la signalisation du FGF. Ces méthodes consistent également à mettre une cellule réagissant au FGF en contact avec un composé exogène modifié par Sulf1, ce dernier étant caractérisé par sa capacité à réduire la liaison de FGF2 ou de FGF4 à FGFR1. L'invention concerne également des compositions qui comprennent les composés exogènes modifiés par Sulf1, lesquelles sont destinées à être utilisées conjointement avec les méthodes selon l'invention.

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