[Identification of novel subtype selective RAR agonists]
>>Biochem Pharmacol. 2005 Nov 18; [Epub ahead of print]
Identification of novel subtype selective RAR agonists.
Piu F, Gauthier NK, Olsson R, Currier EA, Lund BW, Croston GE, Hacksell U, Brann MR.
ACADIA Pharmaceuticals Inc., San Diego, CA, USA.
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.<<
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