Recent advances in the development of retinoids

Retinoic acid (RA) is a metabolite of retinol (vitamin A) which is necessary for a number of biological functions including the maintenance of growth and epithelial cell differentiation. It appears that most of these functions are mediated through formation of a complex with nuclear retinoid receptors which act in a steroid hormone-like mechanism. RA and its analogs (retinoids) have found use in treating dermatological diseases and show promise as cancer chemopreventive/chemotherapeutic agents because of this impact on epithelial tissue differentiation. RA is extensively metabolized and this has a profound impact on its actions and activity. Thus, a reasonably detailed discussion of the quantitatively and/or biologically important metabolites of RA is provided as well as molecular design efforts to inhibit metabolic inactivation processes and stabilize metabolic activation products. The review is concluded with a description of current efforts in the development of more heavily structurally modified analogs, particularly those with nuclear retinoid receptor or receptor subtype specificity.