Orphan nuclear receptors, PXR and LXR: new ligands and therapeutic potential.
Found in almost all animal species, orphan nuclear receptors (NRs) represent a unique and pivotal resource to uncover new regulatory systems that impact on both health and human diseases. Some of the current marketed drugs are known to target orphan NRs. Examples include the anticancer and retinoic X receptor (RXR)-targeting bexarotene (Targretin, Ligand Pharmaceuticals, Inc.) and the antidiabetic and peroxisome proliferator-activated receptor (PPAR)-gamma-targeting thiaozolidinediones. Several studies presented at a recent conference (Orphan and Nuclear Receptors - New Therapeutic Developments) have provided new insights into several orphan NRs, including the pregnane X receptor (PXR), the liver X receptor (LXR), the constitutive androstane receptor (CAR), PPAR and the RXR. This paper will focus on PXR and LXR, whose recent target gene analysis and ligand identification have raised both promises and practical concerns as to whether or not these receptors can be used as therapeutic targets.
University of Pittsburgh, Center for Pharmacogenetics, PA 15261, USA. wex6@pitt.edu
Haibiao
H
Gong
Wen
W
Xie
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy; D041781:Jaundice, Obstructive / Q000188:drug therapy; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D011987:Receptors, Steroid / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000494:pharmacology
D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015262:Xenobiotics; D002784:Cholesterol