Cardarine (GW-501516)

What it is

Cardarine (GW-501516) is an experimental oral compound that GlaxoSmithKline and Ligand Pharmaceuticals developed from the 1990s as a candidate treatment for dyslipidemia (abnormal blood lipids) and metabolic disease. In short human trials it raised HDL ("good") cholesterol, lowered triglycerides and LDL, and increased fat burning, and in rodents it dramatically increased running endurance — which is why it became known as "Endurobol" or an "exercise in a pill." GlaxoSmithKline terminated the program in 2007. The reason later became public: long-term (two-year) carcinogenicity studies showed the drug caused tumors to form rapidly across many organs in both rats and mice. As a result it was never approved anywhere, has no legitimate medical use, and today circulates only as an unapproved black-market bodybuilding and endurance "research chemical." It is banned in sport at all times, and anti-doping agencies have issued the rare step of a direct public health warning about it.

How it works

Cardarine is a high-affinity, subtype-selective synthetic agonist of PPARδ (peroxisome proliferator-activated receptor delta / PPARβ/δ), with a binding affinity of roughly 1 nM and more than 1,000-fold selectivity over the related PPARα and PPARγ receptors. PPARδ is a ligand-activated nuclear receptor (a transcription factor). When Cardarine binds and activates it, it upregulates gene programs that increase fatty-acid oxidation, mitochondrial function and a metabolic shift toward using fat for fuel in skeletal muscle, and it promotes reverse cholesterol transport (e.g. ABCA1 expression) — the basis of the observed rise in HDL, the drop in triglycerides, and the endurance effect seen in rodents. Critically, it does NOT bind or activate the androgen receptor, so it produces none of the direct muscle-building androgenic signaling that defines a true SARM. The same PPARδ pathway is also implicated in tumor-cell proliferation and metabolism, which is the leading mechanistic explanation for its carcinogenicity; the precise pro- versus anti-cancer role of PPARβ/δ in humans remains scientifically unsettled.

Efficacy — what the human evidence shows

The Institute grades each claimed effect by the strength of the human evidence behind it. Grades are assigned independently for benefit and for harm.

Safety signals

Harm signals are reported prominently even where the evidence grade is low. Absence of evidence is not evidence of safety.

Human trials on record

Legal & regulatory status

The bottom line

Cardarine (GW-501516) is not a SARM — it is a PPARδ agonist / metabolic modulator with no androgen-receptor activity. In short human trials it reliably improved cholesterol and metabolic markers, which is why it was originally a promising cardiometabolic drug. But GlaxoSmithKline permanently killed the program in 2007 after two-year rodent carcinogenicity studies — the standard preclinical cancer test — showed it caused tumors rapidly across multiple organs (liver, stomach, bladder, skin, tongue, reproductive organs and more) in both rats and mice. It has never been approved for human use, will never be approved (WADA's own words), and no human data exists on long-term safety because no exposure exceeded roughly 12 weeks. The endurance and fat-loss reputation that drives its grey-market sale rests on rodent studies, not human trials. This is a compound with a documented, serious carcinogenicity signal and no legitimate medical use; it is banned in sport at all times and sold only as an unapproved research chemical.

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