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Literature DB >> 9258350

Identification of highly potent retinoic acid receptor alpha-selective antagonists.

M Teng¹, T T Duong, A T Johnson, E S Klein, L Wang, B Khalifa, R A Chandraratna.

Abstract

The syntheses and full retinoid receptor characterization of a novel series of retinoic acid receptor alpha (RAR alpha) antagonists, 1-5, are described. These compounds bind with high affinity to RAR alpha but were completely inactive in gene transactivation. They were also potent and effective antagonists of retinoic acid (RA) induced gene transcription at RAR alpha. Compounds 1-5 exhibited varying degrees of selectivity for RAR alpha relative to RAR beta/gamma, with compound 5 being the most selective in both binding and functional antagonism assays. These compounds will be invaluable tools in delineating the physiological roles of RAR alpha in development and in the adult animal and may themselves be useful therapeutic agents in human diseases associated with RAR alpha.

Entities: Chemical Gene Species

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Year: 1997 PMID： 9258350 DOI： 10.1021/jm9703911

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

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Cited

12 in total

1. Stereospecificity of retinol saturase: absolute configuration, synthesis, and biological evaluation of dihydroretinoids.

Authors: Alexander R Moise; Marta Domínguez; Susana Alvarez; Rosana Alvarez; Michael Schupp; Ana G Cristancho; Philip D Kiser; Angel R de Lera; Mitchell A Lazar; Krzysztof Palczewski
Journal: J Am Chem Soc Date: 2008-01-08 Impact factor: 15.419

2. Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity.

Authors: Matthias Muenzner; Neta Tuvia; Claudia Deutschmann; Nicole Witte; Alexander Tolkachov; Atijeh Valai; Andrea Henze; Leif E Sander; Jens Raila; Michael Schupp
Journal: Mol Cell Biol Date: 2013-08-19 Impact factor: 4.272

Identification of highly potent retinoic acid receptor alpha-selective antagonists.

1. Stereospecificity of retinol saturase: absolute configuration, synthesis, and biological evaluation of dihydroretinoids.

2. Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity.

3. Retinoic acid signaling is essential for formation of the heart tube in Xenopus.

4. Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo.

5. Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.

6. Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis.

7. Regulation of skeletal progenitor differentiation by the BMP and retinoid signaling pathways.

8. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells.

9. The molecular basis of the interactions between synthetic retinoic acid analogues and the retinoic acid receptors.

10. Requirement for RAR-mediated gene repression in skeletal progenitor differentiation.