Cardarine gw 50156

The strongest evidence for Cardarine's metabolic effects comes from the same animal studies that halted its clinical development: multi-year rodent trials designed to test long-term safety instead revealed a dose-dependent increase in tumor formation across liver, bladder, stomach, tongue, skin, and other tissues. GlaxoSmithKline discontinued all human trials in 2007 after reviewing these findings, yet the compound remains widely discussed in fitness communities as a performance enhancer.

GW-501516: A PPARδ Agonist Developed for Dyslipidemia That Never Made It Past Phase II

GW-501516 (also sold as Cardarine, GW1516, or Endurobol) is a synthetic small molecule developed by GlaxoSmithKline and Ligand Pharmaceuticals in the 1990s. Its molecular formula is C21H18F3NO3S2, with a molecular weight of 453.49 Da. The compound was designed as a selective agonist of peroxisome proliferator-activated receptor delta (PPARδ), a nuclear receptor that regulates lipid metabolism, glucose homeostasis, and inflammation. The initial therapeutic target was dyslipidemia and metabolic syndrome—conditions marked by abnormal cholesterol and triglyceride levels.

Despite being categorized alongside selective androgen receptor modulators (SARMs) in online markets and research chemical catalogs, GW-501516 does not bind androgen receptors and does not exert androgenic effects. It is a PPARδ ligand with a completely distinct mechanism. The confusion likely arises from its co-marketing with actual SARMs and its use in similar research contexts (body composition, performance enhancement).

Clinical development reached Phase II trials in humans, primarily for dyslipidemia and cardiovascular risk reduction. Those trials were terminated in 2007 following the emergence of cancer signals in long-term rodent toxicology studies. No approved therapeutic use exists for GW-501516 in any jurisdiction. It is explicitly banned by the World Anti-Doping Agency (WADA) and the United States Anti-Doping Agency (USADA). For research purposes only, it remains available through non-pharmaceutical suppliers.

PPARδ Activation and the Fatty Acid Oxidation Switch

GW-501516 works by binding to PPARδ, a ligand-activated transcription factor expressed at high levels in skeletal muscle, cardiac muscle, adipose tissue, liver, and brain. PPARδ is one of three PPAR isoforms (alpha, delta, gamma), each with tissue-specific roles in metabolic regulation. PPARδ is the most widely distributed and is strongly implicated in energy substrate selection—that is, whether a cell burns glucose or fat.

When GW-501516 binds to PPARδ, the receptor undergoes a conformational change that allows it to heterodimerize with retinoid X receptor (RXR) and bind to specific DNA sequences called PPAR response elements (PPREs) in the promoter regions of target genes. This binding event upregulates genes involved in fatty acid oxidation, mitochondrial biogenesis, and oxidative metabolism. Key targets include CPT1 (carnitine palmitoyltransferase 1), which shuttles fatty acids into mitochondria; PDK4 (pyruvate dehydrogenase kinase 4), which inhibits glucose oxidation; and UCP2/UCP3 (uncoupling proteins), which influence metabolic efficiency.

In skeletal muscle, PPARδ activation shifts fiber-type composition toward slow-twitch, oxidative (type I) fibers and increases the expression of proteins that support sustained energy output. In adipose tissue, it promotes lipolysis and increases the expression of genes associated with thermogenesis. The net result is a systemic shift toward fat catabolism and away from carbohydrate reliance.

PPARδ also modulates inflammatory signaling pathways. Activation has been shown to suppress NF-κB and reduce the production of pro-inflammatory cytokines such as TNF-α and IL-6 in macrophages and endothelial cells. This anti-inflammatory component is independent of the metabolic effects and has been studied in the context of vascular injury and neuroinflammation.

Rodent Endurance Gains and Lipid Improvements—Followed by Cancer Signals

The most widely cited study demonstrating GW-501516's effects on endurance is a 2008 paper from the Salk Institute published in Cell. Researchers treated sedentary mice with GW-501516 for four weeks and observed a 68% increase in running time to exhaustion compared to controls. Treated mice also showed increased oxidative muscle fibers, elevated mitochondrial content, and improved glucose tolerance. When combined with exercise training, the effect was enhanced further, suggesting a synergy between PPARδ activation and physical activity.

In separate rodent studies focused on dyslipidemia, GW-501516 improved serum lipid profiles. Treated animals showed reductions in triglycerides, LDL cholesterol, and markers of insulin resistance, with concurrent increases in HDL cholesterol. These findings translated into early-phase human trials: a Phase II study in obese men with dyslipidemia showed dose-dependent increases in HDL cholesterol and reductions in triglycerides after 12 weeks of treatment. No serious adverse events were reported in the short-term human trials.

However, long-term safety studies in rodents conducted by GlaxoSmithKline revealed a reproducible carcinogenic signal. In a two-year rat study, GW-501516-treated animals developed tumors in multiple tissues, including the liver, bladder, stomach, skin, and tongue. The tumor incidence was dose-dependent and appeared at doses within the range tested in human trials when adjusted for body surface area. Tumors appeared across multiple organ systems, suggesting a systemic, rather than tissue-specific, carcinogenic mechanism.

The mechanism behind the cancer risk is not definitively resolved. One hypothesis is that chronic PPARδ activation promotes cellular proliferation and reduces apoptosis in already-damaged cells, lowering the threshold for malignant transformation. Another is that the metabolic shift induced by PPARδ may favor the survival and expansion of certain tumor types that rely on oxidative metabolism. Importantly, these findings emerged only after prolonged exposure—short-term human studies did not capture this signal because they were not designed to detect long-term carcinogenesis.

No human data on long-term safety or cancer risk exists. All clinical trials were halted before any study reached a duration long enough to assess chronic toxicity.

Research Dosing, Half-Life, and Administration Parameters from the Literature

In published rodent studies, effective doses of GW-501516 ranged from 2.5 to 10 mg/kg/day, typically administered orally via gavage. For a 25 g mouse, this translates to approximately 0.06 to 0.25 mg per animal per day. When scaled allometrically to a 70 kg human using body surface area conversion (the standard method for interspecies dose translation), these doses correspond to a human equivalent dose range of roughly 10 to 40 mg/day.

In the Phase II human trial for dyslipidemia, doses ranged from 2.5 to 10 mg/day, administered orally once daily. The pharmacokinetic profile in humans shows an elimination half-life of approximately 16 to 24 hours, which supports once-daily dosing. Plasma concentrations reach steady state within 5 to 7 days of consistent administration.

GW-501516 is orally bioavailable and does not require injection. It is lipophilic and absorbed efficiently in the gastrointestinal tract. Stability data from supplier certificates of analysis suggest the compound is stable when stored as a powder at -20°C and protected from light and moisture. Once reconstituted in solution (typically in DMSO, PEG, or ethanol for in vitro work), stability decreases and repeated freeze-thaw cycles degrade potency.

No clinically significant drug-drug interactions have been documented in human trials, though the dataset is small. In vitro studies suggest GW-501516 does not significantly inhibit or induce major cytochrome P450 enzymes at therapeutic concentrations, reducing the likelihood of metabolic interactions with co-administered drugs.

One rodent study suggested that combining GW-501516 with exercise training produced greater endurance gains than either intervention alone, hinting at a synergistic effect when metabolic activation is paired with physical stress. No comparable human data exists.

FAQ

Q: Is Cardarine a SARM?

No. GW-501516 is a PPARδ agonist, not a selective androgen receptor modulator. It does not bind to androgen receptors and does not produce androgenic effects. The confusion arises from its co-marketing in online research chemical markets alongside actual SARMs, but the mechanisms are entirely distinct.

Q: Why was GW-501516 discontinued in human trials?

GlaxoSmithKline halted all clinical development in 2007 after two-year rodent toxicology studies showed dose-dependent tumor formation across multiple organ systems. The cancer signal was consistent and reproducible, appearing at doses within the range tested in early human trials when adjusted for body surface area. No human trials were conducted long enough to assess whether the same risk exists in humans.

Q: What is the evidence quality for Cardarine's endurance effects?

The endurance effects are supported by multiple controlled rodent studies showing increased running capacity, shifts toward oxidative muscle fibers, and improved mitochondrial biogenesis. There are no controlled human trials testing endurance or performance outcomes. The human evidence is limited to short-term Phase II trials focused on lipid profiles, not athletic performance.

Q: How long does GW-501516 stay active in the body?

In humans, the elimination half-life is approximately 16 to 24 hours, based on Phase II pharmacokinetic data. This supports once-daily oral dosing. Steady-state plasma concentrations are reached within about one week of consistent dosing.

Q: Can Cardarine be detected in drug tests?

Yes. WADA added GW-501516 to the prohibited substances list in 2009 and has since developed detection methods for it. Multiple athletes have tested positive for the compound in urine samples, and detection windows can extend several weeks after cessation depending on dose and duration of use. It is banned in all competitive sports governed by WADA and USADA.

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The information provided is for educational and research purposes only and is not intended to diagnose, treat, cure, or prevent any disease. GW-501516 is not approved for human use and carries unresolved safety concerns, including evidence of carcinogenicity in long-term animal studies.