GW 501516

GW-501516 (also known as GW-501,516,GW1516 or GSK-516) is a PPARδ modulator compound being investigated for drug use by GlaxoSmithKline. It activates the same pathways activated through exercise, including PPARδ and AMP-activated protein kinase. It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone.

GW-50156 regulates fat burning through a number of widespread mechanisms ; it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization., This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar. GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity

It has been demonstrated at oral doses of 5 mg a day to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation. Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans.

Concerns were raised prior to the 2008 Beijing Olympics that GW-501516 could be used by athletes as a performance enhancing drug which was not currently controlled by regulations or detected by standard tests. One of the main researchers from the study on enhanced endurance consequently developed a urine test to detect the drug, and made it available to the International Olympic Committee. The World Anti-Doping Agency has also begun work on a test GW-501516 and other related PPARδ modulators., and they have been added to the prohibited list from 2009 onwards. The compound has yet to be named a controlled or prohibited substance by any nation's drug enforcement or regulation agency. To date, no athlete is known to have tested positive for the substance, though the increase in endurance, muscle fiber performance, fat loss and metabolism suggests GW-501516 has the potential for ergogenic use and abuse.