Figure 1.

Chemical structures of natural and representative synthetic retinoids. Retinyl esters (mainly retinyl palmitate; R, fatty acid), stored in the liver stellate cells, are hydrolyzed to retinol, which is then transported to target cells through the circulation after binding to retinol‐binding protein. Retinoic acid (RA) is biosynthesized from retinol via the intermediate metabolite retinal by oxidization in the cells of peripheral tissues. Three well‐known isomers of RA, all‐trans RA, 9‐cis RA, and 13‐cis RA activate the retinoid receptor retinoic acid receptor (RAR), whereas only 9‐cis RA activates the other receptor, retinoid X receptor (RXR). A number of synthetic retinoids have been developed to carry out their pharmacological applications including cancer chemoprevention. Acyclic retinoid and N‐(4‐hydroxyphenyl) retinamide (4HPR) successfully prevented the development of hepatocellular carcinoma and breast cancer, respectively, in clinical trials (see review reference^{( 27 )}).