GW-1516 (aka GW-501,516,GW501516 or GSK-516)

GW 1516 is often used in a "synergistic" combo with Aicar. Is it worth anything for bodybuilders. What do the analyses of black market analyses say. These chemicals are yet very hot and many "research chemicals" rave about it on forums (often as the sponsor). But is a fat or does it contribute to our chemical toolbox?

GW-1516 (also known as GW-501,516,GW501516 or GSK-516) is a PPAR 948; modulator compound being investigated for drug use by GlaxoSmithKline.[1][2] It activates the same pathways activated through exercise, including PPAR 948; and AMP-activated protein kinase. It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. [3] [4] 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. [5][6]

GW-50156 regulates fat burning through a number of widespread mechanisms [7]; it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization.,[8][9] [10] 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. [11] 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 [12]

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.[13] 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. [14]

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.[15] The World Anti-Doping Agency has also begun work on a test GW-501516 and other related PPAR***948; modulators.,[16] and they have been added to the prohibited list from 2009 onwards.[17] 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.

Dosing and usage

We get mixed information regarding dosage of GW-501516  - One site states 5mg to 10mg a day while other sites state and show test results on 2mg to 5mg /kg the most stated //www.ncbi.nlm.nih.gov/pmc/articles/PMC2706130/

AICAR & GW1516

AICAR (500mg/kg/day)  - //www.ncbi.nlm.nih.gov/pmc/articles/PMC2706130/

GW-501516 ( 5 mg/kg/day)  - //www.ncbi.nlm.nih.gov/pmc/articles/PMC2706130/

Depending the results you want – one is to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome

and the other is to improve total endurance and increases muscle mass.

For what we have seen thusfar we have determined that the cost per mg outweighs the effects it should give us ..   Save your money!

"GW501516" - Reduces fat & greatly produces slow twitch muscle

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.

Analyses

Some analytical researchers bought three substances: Aicar, GW1516 and MK-2866. The contents of the bottles that they studied in the lab did contain the right ingredients

The researchers do not reveal the research chemicals webshop where they bought the substances – and we don't know which one it was either. Drug Test Anal. 2011 May;3(5):331-6.

Aicar is a new endurance drug. It's an AMPK booster. If you give the stuff to inactive mice, their endurance increases by 44 percent. [Cell. 2008 Aug 8;134(3):405-15.] It's pretty much an open secret that athletes use Aicar. The French police first discovered it in 2009 in the lockers of cyclists in the Tour de France. [BMJ. 2009 Oct 13; 339:b4201.]

GW1516 comes from the same set-up as Aicar: the molecular researcher Ron Evans. GW1516 is a PPAR-delta-agonist. If you give Aicar to mice their muscle cells burn radically more fat. If you give mice Aicar and GW1516, they reinforce each other's effect and the lab animals turn into ultra-marathon mice. And an interesting detail: some research chemicals shops give a reduction if you buy GW1516 together with Aicar.

The GW1516 contained a warning, the researchers write. "GW501516 is a very potent chemical. This form is for research/laboratory use only. Not intended for human use. Accidental ingestion could cause increased body temperature, heart palpitations, vomiting, shaking, or even death. Keep out of the reach of children. Protect from light. Store at room temperature."

Finally, MK-2866 is a SARM. You might be familiar with it under the name of  Otarine, the little brother of andarine, alias S4. The researchers had previously tested a vial of S4  (from RUI PRODUCTS) that they had bought online, and discovered an overdose of S4 with a number of metabolites that had been created during the biosynthesis process, but which the manufacturer had forgotten to remove. The ostarine that the researchers tested on this occasion was clean, however.

The researchers don't know whether MK-2866 is already being used. They have their suspicions, as S4 has already shown up in doping tests. Last year doping hunters found S4 in a urine sample from the Jamaican Bobby-Gaye Wilkins. [Jamaica Observer 14 July 2010] S4 is unlikely to be launched officially. The company behind S4 stopped tests on the substance a couple of years ago.

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."

(source: GM 'marathon' mice break distance records - 23 August 2004 - New Scientist )

Product Literature References
Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells: T. Coll, et al.; Endocrinology 151, 1560 (2010), Abstract;
Activation of PPARdelta promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated beta-cells: L. Jiang, et al.; Mol.Cell Biol. (2010), Abstract;
Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells: P. Sertznig, et al.; Anticancer Res. 29, 3647 (2009), Abstract;
Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination: A. Defaux, et al.; J. Neuroinflammation 6, (2009), Abstract;
Determination of the critical amino acids involved in the peroxisome proliferator-activated receptor (PPAR) delta selectivity of phenylpropanoic acid-derived agonists: J. Kasuga, et al.; Chem. Med. Chem. 3, 1662 (2008), Abstract;
A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta: Z.L. Wei & A.P. Kozikowski; J. Org. Chem. 68, 9116 (2003), Abstract;
Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)-synthesis and biological activity: M.L. Sznaidman, et al.; Bioorg. Med. Chem. Lett. 13, 1517 (2003), Abstract;
Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism: A.J. Gilde, et al.; Circ. Res. 92, 518 (2003), Abstract;
Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity: Y.X. Wang, et al.; Cell 113, 159 (2003), Abstract;
PPARdelta activation induces COX-2 gene expression and cell proliferation in human hepatocellular carcinoma cells: B. Glinghammar, et al.; BBRC 308, 361 (2003), Abstract;
The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells: U. Dressel, et al.; Mol. Endocrinol. 17, 2477 (2003), Abstract;
A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport: W.R. Oliver, Jr., et al.; PNAS 98, 5306 (2001), Abstract; Full Text