Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
Chemistry. 2009 Nov 2;15(43):11430-42. doi: 10.1002/chem.200901952.
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.
视黄酸信号通路参与细胞中的许多过程，特别是那些介导分化和凋亡的过程。与视黄酸受体结合的内源性配体，即全反式视黄酸（ATRA）和 9-顺式视黄酸，容易发生双键异构化和代谢酶的氧化，这对视黄酸的活性和选择性有显著的有害影响。通过使用合成视黄酸可以克服许多这些问题，合成视黄酸通常更稳定，并且更具活性。对其分子结构的修饰可以得到作为拮抗剂而不是激动剂的视黄酸，或者对特定的视黄酸受体同工型表现出很大的选择性。几种这样的选择性视黄酸可能具有降低毒性的价值，特别是在癌症治疗中，作为控制细胞分化的试剂，以及作为阐明特定视黄酸信号通路在细胞内的确切作用的工具。
