Assays for determining compounds which modulate tram...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/48 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2603868

Disclosed are assays for the determination and quantification of the phosphorylation of TRAM (Trif- related adaptor molecule) . TRAM is rapidly phosphorylated upon LPS stimulation by protein kinase C epsilon (PKC.epsilon.) and that this phosphorylation is vital for TRAM to function normally. Assays suitable for detecting the state of phosphorylation of TRAM have utility in identifying compounds which have activity in modulating TRAM. Further disclosed are compounds which have utility in modulating the phosphorylation of TRAM to modulate signalling mediating by the Toll Like Receptor 4 (TLR4) receptor.

L'invention concerne des dosages pour la détermination et la quantification de la phosphorylation de TRAM (molécule adaptatrice liée à Trif). TRAM est phosphorylée rapidement lors de la stimulation par la protéine kinase C epsilon (PKC.epsilon.), cette phosphorylation étant vitale pour que la TRAM fonctionne normalement. Des dosage convenant à la détection de l'état de phosphorylation de TRAM sont utiles pour identifier des composés ayant une activité dans la modulation de TRAM. L'invention porte également sur des composés utiles dans la modulation de la phosphorylation de TRAM pour moduler la signalisation médiée par le récepteur TLR4 Toll.

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