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Abstract
Retinoids, a group of natural and synthetic retinol (vitamin A) analogues, play an important role in regulating pleiotropic biological events, including growth, differentiation and death of normal, premalignant and malignant cell types, which appears to account for their therapeutic or preventive effects in acne, psoriasis, photoageing, cancer and other diseases. Nuclear retinoic acid receptors and retinoid X receptors are thought to mediate the majority of retinoid biological effects. One effective strategy is to design and synthesise retinoids with receptor selectivity restricted to specific retinoic acid receptors or retinoid X receptor subtypes (α, β and γ) in order to develop novel retinoids with a more favourable therapeutic index and with reduced adverse effects and teratogenic risk. Indeed, retinoid medicinal chemistry has identified ligands that include highly specific antagonists for one of the three RAR subtypes and for retinoid X receptors. Since the retinoid X receptors also serve as heterodimer partners for several other nuclear receptors, including thyroid hormone receptors, vitamin D receptors, peroxisomal proliferator-activator receptors, Farnesoid X receptors and liver X receptors, retinoid X receptor-selective retinoids may have clinical applications for the prevention and treatment of diseases other than dermatological diseases and cancer, such as diabetes, obesity and atherosclerosis.