Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands.

Article Details

Citation

Lund BW, Knapp AE, Piu F, Gauthier NK, Begtrup M, Hacksell U, Olsson R

Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands.

J Med Chem. 2009 Mar 26;52(6):1540-5. doi: 10.1021/jm801532e.

PubMed ID
19239230 [ View in PubMed
]
Abstract

We recently discovered the isoform selective RAR beta 2 ligand 4'-octyl-4-biphenylcarboxylic acid (3, AC-55649). Although 3 is highly potent at RAR beta 2 and displays excellent selectivity, solubility issues make it unsuitable for drug development. Herein we describe the exploration of the SAR in a biphenyl and a phenylthiazole series of analogues of 3. This ultimately led to the design of 28, a novel, orally available ligand with excellent isoform selectivity for the RAR beta 2.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TretinoinRetinoic acid receptor alphaEC 50 (nM)6.31N/AN/ADetails
TretinoinRetinoic acid receptor betaEC 50 (nM)6.31N/AN/ADetails
TretinoinRetinoic acid receptor betaEC 50 (nM)25.12N/AN/ADetails
TretinoinRetinoic acid receptor gammaEC 50 (nM)50.12N/AN/ADetails