title: Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity.
abstract: The nuclear receptor (NR) superfamily is composed of 48 members in humans and includes receptors for steroid hormones, thyroid hormone, various lipids and oxysterols. This superfamily has been a rich source of drug targets for myriad diseases including inflammation, cancer, and metabolic disorders. Approximately half of the superfamily have well characterized natural ligands whereas the remaining receptors are considered orphan receptors and remain a focus of a number of investigators assessing their ability to be regulated by ligands. Here, we review recent discoveries that yield important insight into the druggability of three orphan nuclear receptors: the retinoic acid receptor-like orphan receptors (RORs), peroxisome proliferator-activated receptor γ (PPARγ), and liver receptor homolog-1 (LRH-1).
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA. tburris@scripps.edu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Burris
authors.forename: Scott A
authors.initials: SA
authors.lastname: Busby
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Griffin
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013261:Sterols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C082631:NR5A2 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D010713:Phosphatidylcholines; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D013261:Sterols; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione