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Background And Regulatory History — Background and Details

By Editorial Desk · published 2026-04-29 · last reviewed 2026-05-14 · Info

The short version of Nuclear receptor fits in a sentence. The long version — which is the one that helps — is below.

Reviewed 2026-05-14. Anything still debated is marked as such rather than presented as settled.

Background and Regulatory History

Regulatory bodies treat GW501516 as a prohibited substance in competitive sport. The World Anti-Doping Agency added it to the prohibited list, and it falls under classes covering metabolic modulators and hormone-related agents. It is not approved by drug regulators for human use, and it is not a lawful dietary supplement. Products sold under the cardarine name may contain unlisted ingredients or different compounds. Because no approved product exists, quality and identity are not guaranteed by pharmaceutical manufacturing standards.

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.

Detection, Regulation, and Quality Context

Regulatory treatment of cardarine differs by context and jurisdiction. In competitive sport, the World Anti-Doping Agency lists PPARδ agonists, including GW501516, as prohibited at all times. Outside sport, it lacks approval as a prescription medicine in major drug markets, and products sold for human consumption may be treated as unapproved drugs. Some countries also restrict importation or sale through general consumer protection and medicines laws. These classifications affect availability, testing, and legal risk without establishing therapeutic value.

Because cardarine is not an approved medicine, no pharmacopeial monograph defines its identity, purity, or storage requirements. Laboratories typically rely on in-house methods and reference standards when testing materials labeled as GW501516. Certificates of analysis may report purity and identity for a specific batch, but their scope varies and they do not guarantee safety or legal status. Independent verification can include high-performance liquid chromatography, mass spectrometry, nuclear magnetic resonance, and elemental analysis. The distinction between research chemical labeling and human use is significant because quality standards and oversight differ.

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.

Mechanism and Detection

Anti-doping laboratories identify GW501516 and its metabolites using liquid chromatography-tandem mass spectrometry. Urine is the usual matrix, and detection can occur after the parent compound has cleared from blood. The exact detection window depends on dose, formulation, individual metabolism, and assay sensitivity. Because the compound is prohibited at all times, athletes are subject to testing in and out of competition. Analytical methods continue to improve as new metabolites and designer analogs are characterized.

GW501516 acts as a ligand for PPAR delta, a nuclear receptor that regulates transcription of genes involved in fatty acid oxidation and energy use. Activation of this receptor in skeletal muscle shifts metabolism toward fat burning in animal models. The compound does not burn fat directly; it changes gene expression over hours to days. Researchers study it to understand metabolic flexibility and exercise adaptation. Effects observed in rodents are not automatically expected in humans.

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Mechanism and Safety Research

Literature on cardarine often separates receptor pharmacology from toxicology. Mechanistic papers describe PPARδ activation and gene expression changes, while safety assessments focus on carcinogenicity and species differences. Questions remain about whether rodent tumors arise through PPARδ-dependent or off-target mechanisms. Another open area is how human metabolism and exposure compare with those in animal studies. Analytical methods such as liquid chromatography–mass spectrometry are used to confirm identity in biological and product samples.

GW501516 acts as an agonist at the peroxisome proliferator-activated receptor delta, a nuclear receptor that regulates gene expression. Activation shifts transcription toward genes involved in fatty acid uptake, oxidation, and energy expenditure. The compound does not bind the androgen receptor and therefore differs from anabolic steroids and SARMs. In rodent models, this metabolic shift has been linked to increased running endurance and reduced fat accumulation. The exact downstream pathways in humans remain incompletely characterized.

Reference notes

Full clients verify transactions directly by downloading a full copy of the blockchain. They do not require trust in any external parties. Full clients check the validity of mined blocks, preventing them from transacting on a chain that breaks or alters network rules. Because of its size and complexity, downloading and verifying the entire blockchain is not suitable for all computing devices. Lightweight clients consult full nodes to send and receive transactions without requiring a local copy of the entire blockchain (see simplified payment verification – SPV). This makes lightweight clients much faster to set up and allows them to be used on low-power, low-bandwidth devices such as smartphones. When using a lightweight wallet, however, the user must trust full nodes, as it can report faulty values back to the user. Lightweight clients follow the longest blockchain and do not ensure it is valid, requiring trust in full nodes. Third-party internet services called online wallets or webwallets offer similar functionality but may be easier to use. In this case, credentials to access funds are stored with the online wallet provider rather than on the user's hardware. As a result, the user must have complete trust in the online wallet provider. A malicious provider or a breach in server security may cause entrusted crypto to be stolen. An example of such a security breach occurred with Mt. Gox in 2011.

==== Illegal marketing of Rapamune settlement (2014) ==== A "whistleblower suit" was filed in 2005 against Wyeth, which was acquired by Pfizer in 2009, alleging that the company illegally marketed sirolimus (Rapamune) for off-label uses, targeted specific doctors and medical facilities to increase sales of Rapamune, tried to get transplant patients to change from their transplant drugs to Rapamune, and specifically targeted African Americans. According to the whistleblowers, Wyeth also provided doctors and hospitals that prescribed the drug with kickbacks such as grants, donations, and other money. In 2013, the company pleaded guilty to criminal mis-branding violations under the Federal Food, Drug, and Cosmetic Act. By August 2014, it had paid $491 million in civil and criminal penalties related to Rapamune.

=== Malaysia === According to the Malaysian Food Act 1983 and Regulations (as of 5 January 2010), ractopamine is allowed in pig muscle and fat (MRL of 10 ppb), pig liver (MRL of 40 ppb), and pig kidney (MRL of 90 ppb). Ractopamine is allowed as its half-life is lower, leading to reduced residues in the food, and the dose required to affect humans is much higher than other beta agonists. On 30 December 2008, the Malaysian Veterinary Services Department quarantined 10 of the 656 pig farms in Malaysia, as the livestock were found to contain the banned chemical.

=== Use in molecular biology === Because RIP is so efficient at detecting and mutating repeats, biologists working on Neurospora crassa have used it as a tool for mutagenesis. A second copy of a single-copy gene is first transformed into the genome. The fungus must then mate and go through its sexual cycle to activate the RIP machinery. Many different mutations within the duplicated gene are obtained from even a single fertilization event so that inactivated alleles, usually due to nonsense mutations, as well as alleles containing missense mutations can be obtained.

Sources: en.wikipedia.org

Reference notes

=== First aid === Pre-hospital care for lung barotrauma includes basic life support of maintaining adequate oxygenation and perfusion, assessment of airway, breathing and circulation, neurological assessment, and managing any immediate life-threatening conditions. High-flow oxygen up to 100% is considered appropriate for diving accidents. Large-bore venous access with isotonic fluid infusion is recommended to maintain blood pressure and pulse.

=== Polycythemia in adults === Different diseases or conditions can cause polycythemia in adults. These processes are discussed in more detail in their respective sections below. Relative polycythemia, also known as pseudopolycythemia, is not a true increase in the number of red blood cells or hemoglobin in the blood, but rather an elevated laboratory finding caused by reduced blood plasma (hypovolemia, cf. dehydration). Relative polycythemia is often caused by loss of body fluids, such as through burns, dehydration, and stress. A specific type of relative polycythemia is Gaisböck syndrome; in this syndrome, primarily occurring in obese men, hypertension causes a reduction in plasma volume, resulting in (amongst other changes) a relative increase in red blood cell count. If relative polycythemia is deemed unlikely because the patient has no other signs of hemoconcentration and has sustained polycythemia without clear loss of body fluids, the patient likely has absolute or true polycythemia. Absolute or true polycythemia (also erythrocytosis) can be split into two categories:

=== Use of DNA mismatch-binding proteins === DNA mismatch-binding proteins can distinguish single nucleotide mismatches and thus facilitate differential analysis of SNPs. For example, MutS protein from Thermus aquaticus binds different single nucleotide mismatches with different affinities and can be used in capillary electrophoresis to differentiate all six sets of mismatches.

Concentrated or strong bases are caustic on organic matter and react violently with acidic substances. Aqueous solutions or molten bases dissociate into ions and conduct electricity. Reactions with indicators: bases turn red litmus paper blue, phenolphthalein pink, keep bromothymol blue in its natural colour of blue, and turn methyl orange-yellow. The pH of a basic solution at standard conditions is greater than seven. Bases are bitter.

=== Reading room === The original Reading Room was founded in August 1935 to entertain unemployed workers during the Great Depression. Started as an initiative by the New York Public Library, the Reading Room provided the jobless with a place to interact and share ideas without having to pay money or show identification. Despite this, the library was well-used, being used by 50,000 people by its first anniversary. Theft was low, with only 34 publications being lost in the library's first year. By its third year, 400 books and 1,000 magazines were in circulation and were being perused by 70,000 people per year. Books from the NYPL, and donations of magazines and trade publications from publishers, contributed to the success of the open-air library. The tradition of Reading Rooms halted in 1944 due to a staff shortage during World War II. The Reading Room tradition was revived in 2003 with HSBC as its first sponsor. Oxford University Press, Scholastic Corporation, Mitchell's NY, Condé Nast Publications, Time Inc., Hachette Filipacchi Media U.S., and Rodale, Inc. were among the companies who donated books and publications. In addition to the complimentary reading materials, in 2004 programming was added to Reading Room's content. The Reading Room features readings and book sales by contemporary writers and poets, plus book-related special events such as book clubs, writers workshops and storytelling for kids.

Sources: en.wikipedia.org

Notes from published material

== Other Branded Generics == Biqi is the brand name for its generic OTC anti-diarrhea pharmaceutical. The Company obtained approval to manufacture and sell Biqi in November 1999. Zaiqi is the brand name for the company's azithromycin granules antibiotics for the treatment of infections. Zaike is the brand name for its cefaclor in dry suspension antibiotics for the treatment of infections. Simcere Kechuanning is the brand name for Simcere Pharmaceutical's OTC herbal medicine used for the treatment of coughs. It comes in oral liquid and tablet formulations. Zaikang is the brand name for its OTC compound zinc gluconate and ibuprofen granules for the treatment of cold symptoms, such as fever, nasal congestion, running nose and sneezing. Faneng is the brand name for the company's alfacalcidol soft capsules for the treatment of osteoporosis.

Thus, while in vitro receptor binding affinities, efficacies, and average concentrations in tissue or plasma are useful, they are not likely to predict DMT concentrations in the vesicles or at synaptic or intracellular receptors. Under these conditions, notions of receptor selectivity are moot, and it seems probable that most of the receptors identified as targets for DMT (see above) participate in producing its psychedelic effects. DMT produces the head-twitch response (HTR), a behavioral proxy of psychedelic-like effects, in rodents. However, its effects in the HTR paradigm in mice that are highly strain-dependent, including producing an HTR comparable to other psychedelics, producing an HTR that is much weaker than that of other psychedelics, or producing no HTR at all. These conflicting results may be due to rapid metabolism of DMT and/or other peculiarities of DMT in different species. Besides the HTR, DMT also substitutes for LSD and DOM in rodent drug discrimination tests. DMT has been found to increase oxytocin levels in humans. It is thought that the rate at which DMT enters the brain, and hence its route of administration, may influence its effects, with more rapid routes like intravenous administration and inhalation potentiating serotonin 5-HT2A receptor activation and consequent hallucinogenic effects. As an example, a bolus intravenous injection of 15 mg DMT produces stronger peak effects than a continuous infusion of 1 mg/minute given over 1.5 hours in spite of the latter achieving higher peak DMT levels.

Keuning S, Janssen DB, Witholt B (1985). "Purification and characterization of hydrolytic haloalkane dehalogenase from Xanthobacter autotrophicus GJ10". J. Bacteriol. 163 (2): 635–9. doi:10.1128/JB.163.2.635-639.1985. PMC 219169. PMID 4019411. Scholtz R, Leisinger T, Suter F, Cook AM (1987). "Characterization of 1-chlorohexane halidohydrolase, a dehalogenase of wide substrate range from an Arthrobacter sp". J. Bacteriol. 169 (11): 5016–21. doi:10.1128/jb.169.11.5016-5021.1987. PMC 213902. PMID 3667524. Yokota T, Omori T, Kodama T (1987). "Purification and properties of haloalkane dehalogenase from Corynebacterium sp. strain m15-3". J. Bacteriol. 169 (9): 4049–54. doi:10.1128/jb.169.9.4049-4054.1987. PMC 213707. PMID 3624201. Poelarends GJ, van Hylckama Vlieg JE, Marchesi JR, Freitas Dos Santos LM, Janssen DB (1999). "Degradation of 1,2-dibromoethane by Mycobacterium sp. strain GP1". J. Bacteriol. 181 (7): 2050–8. doi:10.1128/JB.181.7.2050-2058.1999. PMC 93616. PMID 10094681. Poelarends GJ, Wilkens M, Larkin MJ, van Elsas JD, Janssen DB (1999). "Degradation of 1,3-dichloropropene by pseudomonas cichorii 170". Appl. Environ. Microbiol. 64 (8): 2931–6. doi:10.1128/AEM.64.8.2931-2936.1998. PMC 106795. PMID 9687453. Nagata Y, Miyauchi K, Damborsky J, Manova K, Ansorgova A, Takagi M (1997). "Purification and characterization of a haloalkane dehalogenase of a new substrate class from a gamma-hexachlorocyclohexane-degrading bacterium, Sphingomonas paucimobilis UT26". Appl. Environ. Microbiol. 63 (9): 3707–10. Bibcode:1997ApEnM..63.3707N. doi:10.1128/AEM.63.9.3707-3710.1997.

The electron capture detector is used for detecting electron-absorbing components (high electronegativity) such as halogenated compounds in the output stream of a gas chromatograph. The ECD uses a radioactive beta particle (electron) emitter in conjunction with a so-called makeup gas flowing through the detector chamber. The electron emitter typically consists of a metal foil holding 10 millicuries (370 MBq) of the radionuclide 63Ni. Usually, nitrogen is used as makeup gas, because it exhibits a low excitation energy, so it is easy to remove an electron from a nitrogen molecule. The electrons emitted from the electron emitter collide with the molecules of the makeup gas, resulting in many more free electrons. The electrons are accelerated towards a positively charged anode, generating a current. There is therefore always a background signal present in the chromatogram. As the sample is carried into the detector by the carrier gas, electron-absorbing analyte molecules capture electrons and thereby reduce the current between the collector anode and a cathode. Over a wide range of concentrations the rate of electron capture is proportional to the analyte concentration. ECD detectors are particularly sensitive to halogens, organometallic compounds, nitriles, or nitro compounds.

=== Disability === Emotional mental disorders are a leading cause of disabilities worldwide. Investigating the degree and severity of untreated emotional mental disorders throughout the world is a top priority of the World Mental Health (WMH) survey initiative, which was created in 1998 by the World Health Organization (WHO). "Neuropsychiatric disorders are the leading causes of disability worldwide, accounting for 37% of all healthy life years lost through disease. These disorders are most destructive to low and middle-income countries due to their inability to provide their citizens with proper aid. Despite modern treatment and rehabilitation for emotional mental health disorders, "even economically advantaged societies have competing priorities and budgetary constraints".

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 anti-doping tests?

Anti-doping laboratories typically use LC-MS/MS to detect GW501516 and its metabolites in urine. The method is sensitive and can identify the compound at low concentrations. Detection depends on sample timing, metabolism, and the specific assay.

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