Retinoid X receptor ligands: a patent review (2007 - 2013).
BACKGROUND
Retinoid X receptors (RXRs) are nuclear receptors that act as ligand-dependent transcription factors. RXRs function as homodimers or as heterodimers with other nuclear receptors, such as retinoic acid receptors, PPARs, liver X receptors, farnesoid X receptor, vitamin D receptor or thyroid hormone receptors. RXR ligands (agonists or antagonists) show various physiological effects, depending on their partner receptors. RXR agonist bexarotene (Targretin®) is used for the treatment of cutaneous T-cell lymphoma in clinical practice. RXR agonists were also reported to be useful for treatment of type 2 diabetes, autoimmune disease and Alzheimer's disease. RXR antagonists were also reported to be effective in type 2 diabetes treatment.


METHODS
Here patent applications (2007 - 2013) concerning RXR ligands are summarized, and the usefulness of RXR ligands as pharmaceutical agents is discussed.


CONCLUSIONS
RXR agonists show a wide variety of biological effects. However, they cause serious side effects, such as blood triglyceride elevation, hypothyroidism and others. Thus, for clinical application of RXR agonists, abrogation of these side effects is required. RXR heterodimer-selective agonists and RXR partial agonists exhibiting desired effects without side effects are expected to find clinical application.
Okayama University Graduate School of Medicine, Division of Pharmaceutical Sciences, Dentistry and Pharmaceutical Sciences , 1-1-1, Tsushima-Naka, Kita-Ku, Okayama 700-8530 , Japan +81 086 251 7963 ; +81 086 251 7963 ; kakuta-h@cc.okayama-u.ac.jp.
Shoya
S
Yamada
Hiroki
H
Kakuta
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D055808:Drug Discovery; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008024:Ligands; D008516:Medicine, Chinese Traditional; D010330:Patents as Topic; D055503:Protein Multimerization; D047488:Retinoid X Receptors / Q000819:agonists* / Q000737:chemistry
D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008024:Ligands; D047488:Retinoid X Receptors