GW 501516
Encyclopedia
GW-501516 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.
Peroxisome proliferator-activated receptor delta
Peroxisome proliferator-activated receptor beta or delta , also known as NR1C2 is a nuclear receptor that in humans is encoded by the PPARD gene....
modulator compound being investigated for drug use by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
. It activates the same pathways activated through exercise, including PPARδ and AMP-activated protein kinase
AMP-activated protein kinase
5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis. It consists of three proteins that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of...
. It is being investigated as a potential treatment for obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, diabetes, dyslipidemia
Dyslipidemia
Dyslipidemia or dyslipidaemia is an abnormal amount of lipids in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood, often due to diet and lifestyle. The prolonged elevation of insulin levels can lead to dyslipidemia...
and cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
.
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
Glucose uptake
Method of glucose uptake differs throughout tissues depending on two factors; the metabolic needs of the tissue and availability of glucose. The two ways in which glucose uptake can take place are facilitated diffusion and secondary active transport .- Facilitated diffusion :There are over 10...
in skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth 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
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
, 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
International Olympic Committee
The International Olympic Committee is an international corporation based in Lausanne, Switzerland, created by Pierre de Coubertin on 23 June 1894 with Demetrios Vikelas as its first president...
. The World Anti-Doping Agency
World Anti-Doping Agency
The World Anti-Doping Agency , , is an independent foundation created through a collective initiative led by the International Olympic Committee . It was set up on November 10, 1999 in Lausanne, Switzerland, as a result of what was called the "Declaration of Lausanne", to promote, coordinate and...
has also begun work on a test GW-501516 and other related PPARδ
Peroxisome proliferator-activated receptor delta
Peroxisome proliferator-activated receptor beta or delta , also known as NR1C2 is a nuclear receptor that in humans is encoded by the PPARD gene....
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.