Synthetic retinoids and their nuclear receptors.
In addition to all-trans-retinoic acid and its 9 and 13-cis isomers, four synthetic retinoids are currently available to treat diseases of hyperproliferation, such as acne, psoriasis, and actinic keratosis, or cancers such as acute promelocytic leukemia, cutaneous T-cell lymphoma, and squamous or basal cell carcinoma. The retinoids extert their antiproliferative effects by interacting with their retinoic acid and retinoid X receptors that act as ligand-inducible transcription factors. These homologous receptors function either directly on retinoid response elements or indirectly by modifying the responses of other transcription factors. Their major domains for binding DNA and their ligands have been characterized by either nuclear magnetic resonance spectroscopy or X-ray crystallography. The identification and design of synthetic retinoids are overviewed, as are their selective interactions with specific retinoid receptor subtypes and their clinical effects against cancer. Emphasis is placed on the retinoid X receptors and their ligands.
Dawson
M I
MI
Cancer Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mdawson@burnham.org
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001667:Binding, Competitive; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors