title: Identification of novel subtype selective RAR agonists.
abstract: Drugs targeting retinoid receptors have been developed to treat a variety of therapeutic indications, but their success has been limited in part due to lack of selectivity. A novel functional cell-based assay R-SATtrade mark was employed to screen a small molecule chemical library and identify a variety of novel RAR agonists with various subtype selectivities, including RARbeta/gamma and RARgamma selective agonists. A novel class of synthetic compounds that distinguishes between the different RARbeta isoforms is described. This pharmacophore displays anti-proliferative activity and induces differentiation in a neuronal cell line, consistent with a classical retinoid mechanism of action while providing unique subtype selectivity. These novel subtype selective RAR agonists could serve as powerful tools to probe into subtype and isoform-specific retinoid function.
authors.affiliation: ACADIA Pharmaceuticals Inc., San Diego, CA 92131, USA. fpiu@acadia-pharm.com
authors.forename: Fabrice
authors.initials: F
authors.lastname: Piu
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Gauthier
authors.forename: Roger
authors.initials: R
authors.lastname: Olsson
authors.forename: Erika A
authors.initials: EA
authors.lastname: Currier
authors.forename: Birgitte W
authors.initials: BW
authors.lastname: Lund
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Croston
authors.forename: Uli
authors.initials: U
authors.lastname: Hacksell
authors.forename: Mark R
authors.initials: MR
authors.lastname: Brann
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D016501:Neurites; D018168:Receptors, Retinoic Acid / Q000819:agonists*
chemical_list: D018168:Receptors, Retinoic Acid