GW-501516 PPARδ Modulator Compound

[im83931]

I found this interesting.

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 enfor***ent 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.

Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.

"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.

But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.

Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.

The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.

In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes

So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.

But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.

"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.

It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.

Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes

The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.

Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.

Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.

"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."

Journal reference: Public Library of Science Biology (vol 2, e294)Ref: http://en.wikipedia.org/wiki/GW_501516

[DanB]

it is also banned by wada, so it defo has a use only problem is that legit gw1516 costs thousands per mg and is extremely difficult to produce and majority if not all of stuff on net at moment is bunk, a well known site had compounds including gw1516 and aicar tested from some of main peptide suppliers and it was all bunk

[im83931]

Yeah, another research chem company came out with it today. I did the guinea pig thing with S4 and regretted it. I wont be doing it with this.

[DanB]

i would bet a large amount of money its bunk unless its costing couple grand per mg. . .legit stuff in years to come will be very interesting, but like you said i dont fancy being a guinea pig at moment either

[spywizard]

if all you guys need is a big price tag..

I can hook that up..

point being, even if it has a large price tag does not indicate valid product..

[DanB]

i agree, im saying this because i read on another forum a supplier being asked why he didnt/wouldnt carry it and his response was that it would be far too expensive to be a viable product to stock

[im83931]

No big price tag needed here either. I just found the info interesting.