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Background And Regulatory History — Reference Sheet

By Editorial Desk · published 2026-05-30 · last reviewed 2026-06-13 · Info

This is a working overview of GW501516, written for readers who want more than a one-paragraph summary but less than a textbook.

This page was last updated on 2026-06-13 and is reviewed periodically as new material appears.

Background and Regulatory History

Cardarine is a common name for the investigational chemical GW501516, also written GW-1516. It was developed as a peroxisome proliferator-activated receptor delta agonist for metabolic conditions such as dyslipidemia. Early research focused on lipid handling and energy use in skeletal muscle and other tissues. The compound was never approved as a medicine. In public discussion, it is often grouped with performance-enhancing substances, although its receptor target differs from that of anabolic steroids or selective androgen receptor modulators. Regulatory and health authorities have issued warnings about its use.

GW501516 acts on PPARδ, a nuclear receptor that helps regulate fatty acid oxidation and energy homeostasis. In animal studies, activation of this receptor was associated with increased endurance and changes in lipid metabolism. Human trials examined effects on blood lipids and other metabolic markers, but the compound did not advance to approval. Rodent studies later reported tumors in multiple tissues at doses used in those experiments. Whether those findings translate to human risk remains uncertain, and the clinical relevance of the animal data is still debated.

Mechanism and Laboratory Detection

GW501516 binds and activates PPARδ, a nuclear receptor that influences transcription of genes involved in fatty acid oxidation and energy use. Activation shifts some metabolic pathways in preclinical models, which is why the compound has been studied for lipid disorders and exercise-related endpoints. The exact downstream effects in humans are incompletely mapped. PPARδ is expressed in many tissues, including skeletal muscle, liver, and adipose tissue, so broad activation may have varied consequences. Researchers continue to examine how selective or partial activation might alter the balance between benefits and risks.

Published human data are sparse and mostly come from early-phase trials. Those studies examined short-term changes in lipids, glucose, and exercise capacity, but they were not large enough to establish efficacy or long-term safety. Some animal experiments reported increased running endurance, yet such findings do not prove a performance benefit in people. Anti-doping laboratories detect GW501516 and its metabolites in urine or blood using liquid chromatography-tandem mass spectrometry. Detection windows depend on dose, sample type, and individual metabolism. The method is sensitive enough to identify trace residues in tested samples.

Cardarine at a glance

PropertyValueNotes
Common nameCardarineCommon internet and media name.
Research codeGW501516Also written GW-1516.
Drug classPPARδ agonistNot a selective androgen receptor modulator.
Development statusDiscontinuedClinical development halted after rodent cancer findings.
Regulatory statusProhibited in sportListed by WADA; not approved as medicine.

Regulation and Analytical Detection

Cardarine is prohibited in competitive sport under the World Anti-Doping Agency code, where it is classified as a metabolic modulator. It is not approved as a prescription medicine in the United States, European Union, or other major markets. Regulatory action has focused on its presence in sports and in products marketed as research chemicals. Because it has no accepted medical indication, supply is often unregulated. This status creates legal and safety uncertainties for anyone who encounters the substance.

Anti-doping laboratories detect GW501516 and its metabolites using liquid chromatography-tandem mass spectrometry. Urine is the most common matrix, though blood and dried blood spots may also be used in some programs. Detection depends on factors such as dose, timing, metabolism, and the sensitivity of the assay. Published methods describe limits of detection in the low nanogram per milliliter range for related compounds. Exact detection windows are not fixed for all situations and remain an area of ongoing study.

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Mechanism and Detection Methods

Detection of GW501516 in biological samples generally relies on liquid chromatography coupled with tandem mass spectrometry. Urine is a common matrix in anti-doping analysis, while blood or plasma may be used in research settings. Sample preparation can involve enzymatic hydrolysis, protein precipitation, or solid-phase extraction before instrumental analysis. Because the compound undergoes metabolism, assays may target the parent molecule, one or more metabolites, or both. Detection windows are not fixed; they depend on factors such as dose, route, individual metabolism, and assay sensitivity. Reference standards are required for accurate identification and quantification.

Handling and quality assessment of cardarine reference material follow general laboratory practices for poorly characterized compounds. It typically appears as a white to off-white powder and is sparingly soluble in water but soluble in organic solvents such as dimethyl sulfoxide and ethanol. Storage recommendations usually specify a cool, dry, dark place, with long-term storage at low temperature and desiccation. Purity may be checked by high-performance liquid chromatography with ultraviolet detection, while identity is confirmed by mass spectrometry and nuclear magnetic resonance. No pharmacopeial monograph exists, so reported purity and stability depend on the supplier’s methods.

Reference notes

In humans, melanin is the primary determinant of skin color. It is also found in hair, the pigmented tissue underlying the iris of the eye, and the stria vascularis of the inner ear. In the brain, tissues with melanin include the medulla and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus. It also occurs in the zona reticularis of the adrenal gland. The melanin in the skin is produced by melanocytes, which are found in the basal layer of the epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups produce variable amounts of melanin. The ratio of eumelanin (74%) and pheomelanin (26%) in the epidermis is constant regardless of the degree of pigmentation. Some humans have very little or no melanin synthesis in their bodies, a condition known as albinism. Because melanin is an aggregate of smaller component molecules, there are many different types of melanin with different proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism.

There is great potential for RNA interference (RNAi) to be used therapeutically to reversibly silence any gene. For RNAi to realize its therapeutic potential, small interfering RNA (siRNA) must be delivered to the site of action in the cells of target tissues. But finding safe and efficient delivery mechanisms is a major obstacle to achieving the full potential of siRNA-based therapies. Unmodified siRNA is unstable in the bloodstream, has the potential to cause immunogenicity, and has difficulty readily navigating cell membranes. As a result, chemical alterations and/or delivery tools are needed to safely transfer siRNA to its site of action. The majority of approved agents use N-acetylgalactosamine (GalNAc) conjugation to achieve selective hepatocyte delivery via the asialoglycoprotein receptor (ASGPR), enabling subcutaneous administration. Patisiran (Onpattro), the first approved siRNA drug (2018), instead employs a lipid nanoparticle (LNP) formulation for intravenous delivery.

=== Awards received in the 2010s === Honorary Membership of the Czech Society for Mass Spectrometry; Lifetime Achievement Award in Chromatography by the LC-GC Magazine, Europe; Giorgio Nota Award, Italian Chemical Society; Heyrovsky Medal in Chemical Sciences, Prague, Czech Republic.

Sources: en.wikipedia.org

Reference notes

The Green Chemistry Institute (GCI) supports the "implementation of green chemistry and engineering throughout the global chemistry enterprise." The GCI organizes an annual conference, the Green Chemistry and Engineering Conference, provides research grants, administers awards, and provides information and support for green chemistry practices to educators, researchers, and industry. The GCI was founded in 1997 as an independent non-profit organization, by chemists Joe Breen and Dennis Hjeresen in cooperation with the Environmental Protection Agency. In 2001, the GCI became a part of the American Chemical Society.[1]

Uranium-238 (238U or U-238) is the most common isotope of uranium in nature. It is not fissile, but is fertile: it can capture a slow neutron and after two beta decays become fissile plutonium-239. Uranium-238 is fissionable by fast neutrons, but cannot support a chain reaction because inelastic scattering reduces neutron energy below the range where fast fission of one or more next-generation nuclei is probable. Doppler broadening of 238U's neutron absorption resonances, increasing absorption as fuel temperature increases, is an essential negative feedback mechanism for reactor control. About 99.274% of natural uranium is uranium-238, which has a half-life of 4.463×109 years. Depleted uranium has an even higher concentration of 238U, and even low-enriched uranium (LEU) is still mostly 238U. Reprocessed uranium is also mainly 238U, with about as much uranium-235 as natural uranium, a comparable proportion of uranium-236, and much smaller amounts of other isotopes of uranium such as uranium-234, uranium-233, and uranium-232.

Several previous attempts have been made to create glucose-responsive insulin, with varying degrees of success. In the 2010s, Eli Lilly and Company developed an experimental basal insulin analogue called peglispro (BIL), which showed a prolonged and flat activity profile with hepato-preferential action. Although BIL demonstrated improved glycemic control, reduced nocturnal hypoglycemia, and less weight gain compared to insulin glargine, it was associated with increased liver fat, triglycerides, and liver enzyme levels. Due to these concerns and the uncertain regulatory pathway, Lilly discontinued the development of BIL in 2015. Other experimental analogues that are in development include LAPS Insulin115, an ultralong analogue being researched by Hanmi Pharm, and two basal oral analogues in development by Novo Nordisk, OI338 and OI320.

Sources: en.wikipedia.org

Frequently asked questions

Is cardarine a selective androgen receptor modulator?

No. Cardarine is a PPARδ agonist, while selective androgen receptor modulators act on androgen receptors. The two classes differ in receptor target and downstream effects.

Why did clinical development stop?

Preclinical rodent studies reported cancers, including liver and bladder tumors, at tested doses. The human relevance of those findings is uncertain, but development was discontinued. No approved human product resulted.

Is cardarine approved for medical use?

No. It remains an investigational compound without approved therapeutic labeling. Sports regulators prohibit its use, and health agencies have warned against consuming it.

How is cardarine detected in samples?

Anti-doping and clinical laboratories commonly use liquid chromatography-tandem mass spectrometry. The method can identify GW501516 and its metabolites in urine or blood. Detection depends on sample timing and the amount present.

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