Orphan nuclear receptor
The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.
1. A method of screening a test compound for its ability to activate or inhibit hPXR comprising:
i) preparing an expression vector comprising a sequence encoding a DNA binding domain and a hPXR ligand binding domain having the amino acid sequence of 141-434 of SEQ ID NO: 14;
ii) preparing a reporter construct comprising a DNA binding site recognized by said DNA binding domain operably linked to a reporter gene,
iii) introducing said expression vector and said reporter construct into compatible host cells,
iv) incubating said cells resulting from step (iii) with said test compound, and
v) determining the level of expression of said reporter gene,
wherein enhancement of expression of said reporter gene in the presence of said test compound indicates that said test compound can activate hPXR, and
wherein inhibition of expression of said reporter gene in the presence of said test compound indicates that said test compound can inhibit hPXR.