Retinoids Selective for Retinoid X Receptor Response Pathways

Abstract

Retinoids have a broad spectrum of biological activities and are useful therapeutic agents. Their physiological activities are mediated by two types of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). RARs, as well as several related receptors, require heterodimerization with RXRs for effective DNA binding and function. However, in the presence of 9-cis-retinoic acid, a ligand for both RARs and RXRs, RXRs can also form homodimers. A series of retinoids is reported that selectively activates RXR homodimers but does not affect RAR-RXR heterodimers and thus demonstrates that both retinoid response pathways can be independently activated.