RXR homodimer formation and bridged bicyclic aromatic compounds and their use in regulated gene expression

摘要

The invention provides a method of screening a substance for the ability to affect the formation of a retinoid X receptor homodimer comprising combining the substance and a solution containing retinoid X receptors and determining the presence of homodimer formation. The screening method can be used to determine compounds which selectively activate homodimer formation and heterodimer formation. Also provided is a method of screening a substance for an effect on a retinoid X receptor homodimer's ability to bind DNA comprising combining the substance with the homodimer and determining the effect of the compound on the homodimer's ability to bind DNA. Finally, the invention provides methods of activating retinoid X receptor homodimer formation. Bridged bicyclic aromatic compounds are provided having structure (I); wherein R1, R2, R3, R4, R5 and n are as defined herein. The compounds are useful for modulating gene expression of retinoic acid receptors, vitamin D receptors and thyroid receptors. Pharmaceutical compositions and methods for modulating gene expression are provided as well.