Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands.
Article Details
- CitationCopy to clipboard
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
Drug Target Property Measurement pH Temperature (°C) Tretinoin Retinoic acid receptor alpha EC 50 (nM) 6.31 N/A N/A Details Tretinoin Retinoic acid receptor beta EC 50 (nM) 6.31 N/A N/A Details Tretinoin Retinoic acid receptor beta EC 50 (nM) 25.12 N/A N/A Details Tretinoin Retinoic acid receptor gamma EC 50 (nM) 50.12 N/A N/A Details