Chiral diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex
AssigneeIntrexon Corporation
InventorsRobert Eugene Hormann, Bing Li
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Abstract
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.
Claims15
A method for regulating endogenous or heterologous gene expression in a transgenic subject comprising contacting a ligand with an ecdysone receptor complex within the cells of said subject, wherein said cells further contain a DNA binding sequence for said ecdysone receptor complex when in combination with said ligand and wherein formation of an ecdysone receptor complex-ligand-DNA binding sequence complex induces expression of the gene, and wherein said ligand is 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 endogenous or heterologous gene expression in a transgenic subject is regulated.
A method of regulating transgene expression in a transgenic subject, wherein said transgenic subject comprises a recombinant ecdysone receptor complex capable of regulating transgene expression;
- the method comprising administering to said subject an effective amount of 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.
Dependencies are inferred from the claim text.