Biology and toxicology of PPARgamma ligands.
The peroxisome proliferator activated receptor-gamma (PPARgamma) is an attractive target for therapeutic intervention, as modulation of PPARgamma-regulated pathways is potentially beneficial in a number of disease areas. This review provides an overview of what is known about the biology of PPARgamma, and an indication of what progress has been made towards drug development in several therapy areas. As well as efficacy, the safety of drugs is of course an important issue, and a substantial volume of preclinical and clinical information has already accumulated for PPARgamma agonists. Here we discuss some of the major toxicology issues with PPARgamma agonists, and give a perspective on likely issues concerning the development of PPARgamma modulators in the future.
Tugwood
J D
JD
jonathan.tugwood@astrazenica.com
Montague
C T
CT
D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation; D007333:Insulin Resistance; D008024:Ligands; D008830:Microbodies; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000737:chemistry / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; D008024:Ligands; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione