Cytochrome p450 induction assay

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/68 (2006.01) C12N 5/10 (2006.01) C12N 15/53 (2006.01)

Patent

CA 2577250

A method for identifying compounds that can induce expression of cytochrome P450, in particular, expression of the CYP3A4 isoform, is described. The method provides a reporter gene operably linked to a composite promoter comprising in tandem one or more cis-acting elements, which are bound by activated pregnane X receptor (PXR), operably linked to a heterologous promoter. Analytes, which are inducers CYP3A4 expression via PXR activation, induce expression of the reporter gene.

L'invention concerne un procédé d'identification de composés pouvant induire l'expression de cytochrome P450, en particulier celle de l'isoforme CYP3A4. Le procédé consiste à fournir un gène rapporteur lié opérationnel à un promoteur composite qui présente en tandem un ou plusieurs éléments cis-agissants, liés par un récepteur prégnane X (PXR) activé, lié opérationnel à un promoteur hétérologue. Les analytes, inducteurs de l'expression de CYP3A4 par activation PXR, induisent l'expression du gène rapporteur.

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