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Synthetic Retinoids: Structure–Activity Relationships
Author(s) -
Barnard Jonathan H.,
Collings Jonathan C.,
Whiting Andrew,
Przyborski Stefan A.,
Marder Todd B.
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901952
Subject(s) - retinoid , retinoic acid , retinoid x receptor beta , retinoid x receptor , receptor , retinoid x receptor gamma , biochemistry , chemistry , enzyme , retinoid x receptor alpha , biology , microbiology and biotechnology , nuclear receptor , gene , transcription factor
Retinoid signalling pathways are involved in numerous processes in cells, particularly those mediating differentiation and apoptosis. The endogenous ligands that bind to the retinoid receptors, namely all‐ trans ‐retinoic acid (ATRA) and 9‐ cis ‐retinoic acid, are prone to double‐bond isomerisation and to oxidation by metabolic enzymes, which can have significant and deleterious effects on their activities and selectivities. Many of these problems can be overcome through the use of synthetic retinoids, which are often much more stable, as well as being more active. Modification of their molecular structures can result in retinoids that act as antagonists, rather than agonists, or exhibit a large degree of selectivity for particular retinoid‐receptor isotypes. Several such selective retinoids are likely to be of value as pharmaceutical agents with reduced toxicities, particularly in cancer therapy, as reagents for controlling cell differentiation, and as tools for elucidating the precise roles that specific retinoid signalling pathways play within cells.