Synthetic retinoids: structure-activity relationships. 2009

Jonathan H Barnard, and Jonathan C Collings, and Andrew Whiting, and Stefan A Przyborski, and Todd B Marder
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.

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.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D006860 Hydrogen Bonding A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012176 Retinoids A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization. Retinoid
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D047488 Retinoid X Receptors A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways. Retinoid X Receptor,9-cis-Retinoic Acid Receptor,RXR Protein,Receptor, Retinoid X,XR78E-F protein,Protein, RXR,Receptor, 9-cis-Retinoic Acid,Receptors, Retinoid X,XR78E F protein,protein, XR78E-F
D054314 Drug Inverse Agonism Phenomena and pharmaceutics of compounds that bind to the same receptor binding-site as an agonist (DRUG AGONISM) for that receptor but exerts the opposite pharmacological effect. Inverse Agonism,Inverse Agonist,Inverse Agonists,Agonism, Drug Inverse,Agonism, Inverse,Agonisms, Inverse,Agonist, Inverse,Agonists, Inverse,Inverse Agonism, Drug,Inverse Agonisms
D057927 Hydrophobic and Hydrophilic Interactions The thermodynamic interaction between a substance and WATER. Hydrophilic Interactions,Hydrophilic and Hydrophobic Interactions,Hydrophilicity,Hydrophobic Interactions,Hydrophobicity,Hydrophilic Interaction,Hydrophilicities,Hydrophobic Interaction,Hydrophobicities,Interaction, Hydrophilic,Interaction, Hydrophobic,Interactions, Hydrophilic,Interactions, Hydrophobic
D018168 Receptors, Retinoic Acid Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized. Retinoic Acid Receptors,Retinoic Acid-Binding Proteins,Retinoic Acid Receptor,Proteins, Retinoic Acid-Binding,Receptor, Retinoic Acid,Retinoic Acid Binding Proteins
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

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