Synthetic retinoids: structure-activity relationships.
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.
Barnard
Jonathan H
JH
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
Collings
Jonathan C
JC
Whiting
Andrew
A
Przyborski
Stefan A
SA
Marder
Todd B
TB
D001665:Binding Sites; D018360:Crystallography, X-Ray; D054314:Drug Inverse Agonism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012176:Retinoids / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids