Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells.
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Canan Koch SS, Dardashti LJ, Cesario RM, Croston GE, Boehm MF, Heyman RA, Nadzan AM
Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells.
J Med Chem. 1999 Feb 25;42(4):742-50.
- PubMed ID
- 10052980 [ View in PubMed]
- Abstract
A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of 3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime provides a variety of analogues. Oximes and variously substituted oxime derivatives demonstrate high binding affinity for the RXRs and specific RXR activation and, hence, are called rexinoids. These oxime rexinoids are activators of the RXR:PPARgamma heterodimer and are potent inducers of differentiation of 3T3-L1 preadipocytes to adipocytes. We have recently reported that ligands which activate the RXR:PPARgamma heterodimer in this manner are effective in the treatment of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM). Thus, these new oxime rexinoids are potential therapeutic agents for the treatment of metabolic disorders, such as obesity and diabetes.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Bexarotene Retinoic acid receptor RXR-alpha EC 50 (nM) 28 N/A N/A Details Bexarotene Retinoic acid receptor RXR-alpha Ki (nM) 36 N/A N/A Details Bexarotene Retinoic acid receptor RXR-beta Ki (nM) 21 N/A N/A Details Bexarotene Retinoic acid receptor RXR-beta EC 50 (nM) 25 N/A N/A Details Bexarotene Retinoic acid receptor RXR-gamma EC 50 (nM) 20 N/A N/A Details Bexarotene Retinoic acid receptor RXR-gamma Ki (nM) 29 N/A N/A Details