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Human & Experimental Toxicology
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Biology and toxicology of PPARg ligands

J D Tugwood

AstraZeneca Pharmaceuticals Safety Assessment Group, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK; jonathan.tugwood{at}astrazenica.com

C T Montague

Medical Research Council, Diabetes Research Group, PO Box 19070, Tygerberg, 7505 Cape Town, South Africa

The peroxisome proliferator activated receptor-gamma (PPARg) is an attractive target for therapeutic intervention, as modulation of PPARg-regulated pathways is potentially beneficial in a number of disease areas. This review provides an overview of what is known about the biology of PPARg, 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 PPARg agonists. Here we discuss some of the major toxicology issues with PPARg agonists, and give a perspective on likely issues concerning the development of PPARgmodulators in the future.

Key Words: PPARgamma • thiazolidinediones • Type II diabetes

Human & Experimental Toxicology, Vol. 21, No. 8, 429-437 (2002)
DOI: 10.1191/0960327102ht282oa
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