Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold.
Fiche publication
Date publication
mai 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Martinez C, Lieb M, Alvarez S, Rodriguez-Barrios F, Alvarez R, Khanwalkar H, Gronemeyer H, de Lera AR
Lien Pubmed
Résumé
Arotinoids containing a C5,C8-diphenylnaphthalene-2-yl ring linked to a (C3-halogenated) benzoic acid via an ethenyl connector (but not the corresponding naphthamides), which are prepared by Horner-Wadsworth-Emmons reaction of naphthaldehydes and benzylphosphonates, display the rather unusual property of being RXR agonists (15-fold induction of the RXR reporter cell line was achieved at 3- to 10-fold lower concentration than 9-cis-retinoic acid) and RAR antagonists as shown by transient transactivation studies. The binding of such bulky ligands suggests that the RXR ligand-binding domain is endowed with some degree of structural elasticity.
Référence
ACS Med Chem Lett. 2014 Mar 19;5(5):533-7