Discovery of ligands for the nuclear peroxisome proliferator-activated receptors.
The identification of high-affinity ligands for PPAR gamma has revealed the role of this receptor as the molecular target for the antidiabetic activity of the thiazolidinediones. The surprising observation that agonists of an adipogenic transcription factor reverse the obesity-associated disease of diabetes highlights the power of using potent and selective ligands to study receptor-mediated biology. Similarly, the observation that PGD2 and its cyclopentenone metabolites compounds are microM PPAR ligands suggests that these receptors may have a physiological role in mediating prostaglandin signaling in the spleen.
Willson
T M
TM
Department of Medicinal Chemistry, Glaxo Research Institute, Research Triangle Park, North Carolina 27709, USA.
Lehmann
J M
JM
Kliewer
S A
SA
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011994:Recombinant Proteins; D000077154:Rosiglitazone; D013844:Thiazoles / Q000737:chemistry; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000502:physiology*
D007004:Hypoglycemic Agents; D008024:Ligands; D009687:Nuclear Proteins; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone