Novel Drugs Targeting Retinoic Acid Receptors

Retinoids, essential for various biological processes, regulated gene transcription by binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The discovery of receptor co-regulators advanced retinoid studies. Systemic retinoid therapy was effective for dermatological conditions but had significant side effects. First-generation retinoids like tretinoin, isotretinoin, and alitretinoin had severe toxicities, including teratogenic effects and hair loss. Second-generation retinoids, etretinate and acitretin, were used for psoriasis and other skin disorders, showing effectiveness but also causing mucocutaneous side effects. Etretinate had a long terminal half-life, while acitretin was effective in clinical trials for ichthyosis and keratinization disorders.