GW501516, also known by names like Cardarine and Endurobol, is an experimental drug that has never been approved for human use. It was first developed in the 1990s through a partnership between GlaxoSmithKline and Ligand Pharmaceuticals. The initial goal for the substance was to research its potential for treating metabolic and cardiovascular conditions, such as obesity and diabetes.
Mechanism of Action
GW501516 functions as a selective Peroxisome Proliferator-Activated Receptor delta (PPARδ) agonist. It binds to and activates PPARδ receptors, proteins found in high concentrations in tissues with active metabolism like skeletal muscle, the heart, and the liver. These receptors help regulate energy homeostasis, mitochondrial function, and how the body uses fuel sources. By activating PPARδ, the compound initiates a cascade of genetic changes.
This activation reprograms the body’s energy preferences. It encourages cells, particularly in the muscles, to increase their use of fatty acids for energy instead of relying on glucose. This shift is accomplished by upregulating genes involved in fatty acid oxidation, the process of breaking down fats for fuel.
GW501516 is not a Selective Androgen Receptor Modulator (SARM), although it is frequently miscategorized as one online and in fitness communities. SARMs work by targeting androgen receptors, which are involved with hormones like testosterone. GW501516 operates on an entirely different cellular pathway related to metabolism and energy expenditure.
Reported Effects and Performance Claims
The most widely reported claim associated with GW501516 is a significant enhancement of physical endurance. This metabolic shift could spare glycogen stores, allowing for sustained physical activity over longer periods. Anecdotal reports from users often describe the ability to perform more intense cardiovascular exercise for extended durations.
Another common claim is its effectiveness in promoting fat loss while preserving lean muscle mass. This makes it appealing within bodybuilding circles for “cutting” phases, where the goal is to reduce body fat without losing muscle.
Early research and limited human studies pointed toward potential improvements in cardiovascular health markers. Studies in obese rhesus monkeys and some human trials showed GW501516 could increase high-density lipoprotein (HDL) and lower very-low-density lipoprotein (VLDL). These findings suggested a possible therapeutic use in treating dyslipidemia, a condition characterized by an unhealthy balance of lipids.
Health Risks and Abandoned Research
The development of GW501516 was halted by its creator, GlaxoSmithKline, in 2007 for safety reasons based on the results of preclinical animal studies. These studies, conducted as a standard part of the drug development process, uncovered severe health risks.
Specifically, long-term studies in both mice and rats found that GW501516 caused cancer to develop rapidly and aggressively. The cancers were not isolated to a single area; tumors were observed in multiple organs, including the liver, bladder, stomach, and skin. This indicated a systemic carcinogenic effect, meaning the substance promoted cancer throughout the body.
The cancers developed in a dose-dependent manner. Proponents in online forums often argue that the doses used in these rodent studies were excessively high and not relevant to human use. However, the pharmaceutical developers and regulatory bodies deemed the risk unacceptable, even at lower, potentially therapeutic doses, leading to the complete cessation of all clinical trials.
The evidence from the animal trials is the primary reason GW501516 has not been approved for medical use. The findings demonstrated a clear link between the activation of the PPARδ pathway by this compound and widespread cancer development in animal models.
Legal and Regulatory Status
Globally, no country has approved GW501516 for human use as either a prescription medication or an over-the-counter product. Despite its unapproved status, the substance remains available for purchase through online vendors.
To circumvent laws governing drugs, GW501516 is sold under the guise of a “research chemical.” These products are labeled with disclaimers such as “not for human consumption” or “for laboratory use only.” This labeling creates a legal loophole that allows for its distribution, as it is understood that individuals are purchasing it for personal use.
For athletes, the World Anti-Doping Agency (WADA) has included GW501516 on its Prohibited List. It is classified as a “Hormone and Metabolic Modulator” due to its performance-enhancing capabilities and the serious health risks it poses. WADA has also issued specific public warnings about the dangers of GW501516, highlighting the toxicities found in preclinical studies.