Chiral diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

摘要

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.

主权项

1. A method of modulating the expression of a gene of interest in a host cell, wherein the host cell comprises a first recombinant gene expression cassette comprising a first polynucleotide encoding a first polypeptide comprising:
i) a DNA-binding domain; and ii) a Group H nuclear receptor ligand binding domain;and a second recombinant gene expression cassette comprising:
i) a response element capable of binding to said DNA binding domain; ii) a promoter; and iii) said gene of interest;the method comprising contacting said host cell with a compound selected from the group consisting of:
(R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N′-benzoyl-N-(1-tert-butyl-butyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-methyl-benzoyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-fluoro-benzoyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N′-(2-bromo-benzoyl)-N-(1-tert-butyl-butyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(3-methyl-benzoyl)-hydrazide; (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(4-methyl-benzoyl)-hydrazide; and (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide, wherein the expression of the gene of interest is modulated.