title: Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold.
abstract: 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.
authors.affiliation: Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
authors.forename: Claudio
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS/INSERM/UdS , BP 10142, 67404 Illkirch, Cedex, C. U. de Strasbourg, France.
authors.forename: Michele
authors.initials: M
authors.lastname: Lieb
authors.affiliation: Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Rodríguez-Barrios
authors.affiliation: Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Alvarez
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS/INSERM/UdS , BP 10142, 67404 Illkirch, Cedex, C. U. de Strasbourg, France.
authors.forename: Harshal
authors.initials: H
authors.lastname: Khanwalkar
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS/INSERM/UdS , BP 10142, 67404 Illkirch, Cedex, C. U. de Strasbourg, France.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Gronemeyer
authors.affiliation: Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
authors.forename: Angel R
authors.initials: AR
authors.lastname: de Lera
keywords: Retinoid receptor subtypes; agonists; antagonists; arotinoids; molecular modeling; transactivation