Fiche publication
Date publication
janvier 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Alvarez S, Bourguet W, Gronemeyer H, de Lera AR
Lien Pubmed
Résumé
IMPORTANCE OF THE FIELD: Retinoids are currently used in the clinic for the treatment of skin diseases and acute promielocytic leukemia and are known to contribute to early development and organogenesis in embryo and throughout life. Most of these activities are primarily due to the binding of the retinoid to the retinoic acid receptors (RARs, subtypes alpha, beta and gamma). Ligand modulates, via allosteric conformational changes, the ability of RARs to interact with different sets of co-regulators. Structure-based insights on the ligand-binding domain of the ligand-bound RARs have clearly linked retinoid function to co-activator (CoA) recruitment for agonists, CoA dissociation for antagonists and corepressor stabilization for inverse agonists. AREAS COVERED IN THIS REVIEW: To help understand ligand-modulated RAR action as a consequence of its interaction with different sets of co-regulators, we present the chemical engineering of subsets of retinoid chemotypes (rexinoids, i.e., the ligands of the retinoid X receptors, alpha, beta and gamma, with impact in the treatment of cancer and metabolic diseases, are not covered) that display the whole range of ligand functions, including subtype- and isotype-selectivities. WHAT THE READER WILL GAIN: An understanding of the correlation of retinoid ligand structure and function. Structural insights into ligand action and retinoid chemotypes. Potential for clinical application of retinoid receptor modulators. TAKE HOME MESSAGE: Potential pharmacological/therapeutic applications of these chemical tools extend beyond cancer prevention and therapy to the treatment of autoimmune and neurodegenerative diseases.
Référence
Expert Opin Ther Pat. 2011 Jan;21(1):55-63
