Clinical development plan: 9-cis-Retinoic acid

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 892 KB
• Volume: 63
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240630713

✦ Synopsis

9-cis-Retinoic acid (9-cis-RA) is a stereo-and photoisomer of all-nuns-retinoic acid (all-nuns-RA) [l]. The cancer chemopreventive activities of the all-trans and 1 3 4 s (13-cis-RA) isomers of retinoic acid [2] are well recognized. The biological effects of retinoids are mediated by intracellular receptors, which function as ligand-dependent transcription factors. Retinoid receptors are classified into two subfamilies, RARs and RXRs, based on differences in primary structure, sensitivity to synthetic retinoid ligands, and ability to regulate expression of different target genes [3]. all-h-ans-RA binds directly to, and transcriptionally activates, RARs; however, although it can activate RXRs to regulate expression of target genes, it is not a ligand for the RXR subfamily of receptors [l].

Recently, 9-cis-RA was identified as a high affinity ligand for the RXRs [3,4]; it is up to 40 times more potent than all-fruns-RA in transactivating RXRs. 9-cis-RA also binds to and transactivates RARs, serving as a "bifunctional" ligand [ 13.

RXRs can form homodimers and are capable of acting independently; however, they also form stable