Nuclear receptors as drug targets in metabolic diseases: new approaches to therapy.
Nuclear receptors represent novel targets for the development of therapeutic agents for the treatment of numerous diseases, including type 2 diabetes, obesity dyslipidemia, atherosclerosis and the metabolic syndrome. There have been many recent advances in the development of new therapeutic agents for a subset of these receptors, including the peroxisome proliferator-activated receptors, the liver X receptors and the farnesoid X receptor. To date, the synthesis of selective modulators that regulate the activity of these receptors has been empirical. However, a detailed understanding of the molecular basis for selective modulation, as well as new insights into the biology of these receptors, might open the door to the rational design of a new generation of therapeutic agents with improved safety and efficacy.
Tobin
James F
JF
Department of Cardiovascular and Metabolic Diseases, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. jtobin@wyeth.com
Freedman
Leonard P
LP
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D000071518:Liver X Receptors; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000503:physiopathology; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D016601:RNA-Binding Proteins / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
D004268:DNA-Binding Proteins; C096916:FXR1 protein, human; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear