Details

Autor(en) / Beteiligte

• Lund, Birgitte W
• Piu, Fabrice
• Gauthier, Natalie K
• Eeg, Anne
• Currier, Erika
• Sherbukhin, Vladimir
• Brann, Mark R
• Hacksell, Uli
• Olsson, Roger

Titel

Discovery of a Potent, Orally Available, and Isoform-Selective Retinoic Acid β2 Receptor Agonist

Ist Teil von

• Journal of medicinal chemistry, 2005-12, Vol.48 (24), p.7517-7519

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2005

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 4‘-Octyl-4-biphenylcarboxylic acid (1g, AC-55649) was identified as a highly isoform-selective agonist at the human RARβ2 receptor in a functional intact cell-based screening assay. The subsequent hit to lead optimization transformed the lipophilic, poorly soluble hit into a more potent and orally available compound (2, AC-261066) with retained β2 selectivity and greatly improved physiochemical properties. Being an isoform-selective RARβ2 receptor agonist that discriminates between nuclear receptor isoforms having identical ligand binding domains, 2 will be useful as a pharmacological research tool but also a valuable starting point for drug development.