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Cardarine As Investigational Pparδ Agonist — Practical Notes

By Editorial Desk · published 2025-07-22 · last reviewed 2025-09-11 · Topic

A practical reference on LC-MS/MS: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.

This page was last updated on 2025-09-11 and is reviewed periodically as new material appears.

Cardarine as Investigational PPARδ Agonist

Cardarine is a synthetic compound also known as GW501516, GW-501516, and sometimes endurobol. It was developed as a selective agonist of peroxisome proliferator-activated receptor delta, a nuclear receptor involved in fatty acid oxidation and energy metabolism. The compound was studied in preclinical models for metabolic and cardiovascular conditions, but it did not become a marketed human medicine. In regulatory and anti-doping contexts, it is treated as a prohibited substance rather than a licensed medicine.

The pharmacological interest in cardarine centers on PPARδ activation and its downstream effects on lipid handling and mitochondrial function. In animal studies, PPARδ agonists have been associated with changes in exercise endurance and fatty acid utilization, though results vary by model and protocol. Human data remain sparse, and the absence of large controlled trials limits conclusions about efficacy. Researchers often describe the compound as a tool for probing PPARδ biology rather than a proven therapeutic agent.

Safety discussions about cardarine frequently cite rodent carcinogenicity findings reported in the 2000s. In those studies, treated animals developed tumors at multiple sites, leading sponsors to discontinue clinical development. The relevance of these findings to humans has not been resolved, but they are a major reason the compound is not approved. Current literature emphasizes uncertainty about long-term effects and the risks of unregulated use. Regulators and health agencies have not established a safe human exposure level.

Regulation and Detection

Anti-doping laboratories identify GW501516 and related metabolites using liquid chromatography coupled with tandem mass spectrometry. Urine is the most common matrix, though blood and dried blood spots may also be analyzed. The method targets the parent compound and phase I and phase II metabolites, which extend the detection window. Because the substance is prohibited at all times, athletes can be tested outside competition. Detection limits and windows depend on the assay, sample type, and individual metabolism.

Cardarine is frequently described as a fat-burning or endurance-enhancing supplement, but these claims exceed the available evidence. The compound is not a hormone, steroid, or selective androgen receptor modulator. Research articles discuss it as a tool compound for studying PPARδ biology, while anti-doping literature focuses on its abuse and detection. Quality of unapproved products is uncertain, and independent analyses have found impurities or incorrect labeling. Open questions include whether human cancer risk resembles that seen in rodents and how often non-athletes use the substance.

Cardarine at a glance

PropertyValueNotes
Common synonymsGW501516, GW-501516, GW 501516, endurobolNames vary in research and anti-doping documents.
Chemical classSynthetic PPARδ agonistSmall-molecule nuclear receptor ligand.
CAS Registry Number317318-70-0Identifier commonly associated with GW501516.
AppearanceWhite to off-white powderTypical for purified research material.
SolubilityLow in water; soluble in DMSO and ethanolOrganic solvents are common for laboratory stock solutions.

Identity and Pharmacological Classification

Published studies have examined GW501516 in animal models of obesity, insulin resistance, and exercise endurance. Early human trials reportedly ended, and development was discontinued after preclinical findings raised concerns about cancer in some rodent studies. Regulatory agencies have not approved cardarine for any medical use. Its availability through non-pharmaceutical channels raises questions about identity, purity, and legal status that are separate from its laboratory pharmacology. Those questions are often addressed through analytical testing rather than assumptions about product labels.

Cardarine is a common name for GW501516, also GW-1516, a synthetic compound developed as a peroxisome proliferator-activated receptor delta (PPARδ) agonist. It belongs to a class of agents that modulate gene transcription related to lipid and energy metabolism. The compound was studied in preclinical and early clinical research for metabolic and cardiovascular conditions, but it did not progress to approved therapeutic use. Its name appears in fitness and sports contexts despite not being approved as a drug.

PPARδ is a nuclear receptor that influences transcription of genes involved in fatty acid oxidation, lipid transport, and energy homeostasis. GW501516 binds and activates this receptor with high selectivity relative to PPARα and PPARγ in laboratory assays. Activation alters expression of target genes in skeletal muscle, liver, and adipose tissue in animal models. The exact clinical consequences of these changes in humans remain incompletely characterized, and observed effects in animals do not establish therapeutic benefit or safety.

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Regulation and Analytical Detection

Products sold as cardarine have been found to contain incorrect compounds, variable amounts, or no active ingredient at all. Independent testing is required to verify identity and purity. Common analytical approaches include high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance for structural confirmation. These methods can distinguish GW501516 from related PPAR agonists and from unrelated steroids. For regulators and researchers, such verification is central to interpreting both biological results and adverse event reports.

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.

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.

Notes from published material

== History == Little Caesars Pizza was founded on May 8, 1959, by the married couple Mike Ilitch and Marian Ilitch. The first location was in a strip mall in Garden City, Michigan, a suburb of Detroit, and named "Little Caesar's Pizza Treat". The original store closed in October 2018, relocating down the street to a new building in nearby Westland. The first Little Caesar's franchise location opened in 1962 in Warren, Michigan, and was still called Little Caesar's Pizza Treat. The same year the Little Caesar's logo became a 3D figure and was used in outdoor signage.

== Medicical values == The plants have been known to possess various phytochemicals (secondary metabolites) which help them to protect themselves, these phytoehemicals since time immemorial have been used by humans for their medicinal needs. The microbes are developing resistant again multiple synthetic drugs, thus leading to the emergence of MDR (Multi Drug Resistant) strains of microbes, which pose a challenge to the modern drug system. To overcome this challenge, the nanoparticles synthesized using extracts of plant and plant parts have emerged as a hope. Many workers have reported that the nanoparticles synthesized using plant extracts have shown to exhibit enhanced medicinal properties as compared to the extract(s) alone.

=== Discovery and development === In 1953, Alfred Day Hershey reported that soon after infection with phage, bacteria produced a form of RNA at a high level and this RNA was also broken down rapidly. However, the first clear indication of mRNA was from the work of Elliot Volkin and Lazarus Astrachan in 1956 by infecting E.coli with T2 bacteriophages and putting them into the medium with 32P. They found out that the protein synthesis of E.coli was stopped and phage proteins were synthesized. Then, in May 1961, their collaborated researchers Sydney Brenner, François Jacob, and Jim Watson announced the isolation of mRNA. For a few decades after mRNA discovery, people focused on understanding the structural, functional, and metabolism pathway aspects of mRNAs. However, in 1990, Jon A. Wolff demonstrated the idea of nucleic acid-encoded drugs by direct injecting in vitro transcribed (IVT) mRNA or plasmid DNA (pDNA) into the skeletal muscle of mice which expressed the encoded protein in the injected muscle. Once IVT mRNA has reached the cytoplasm, the mRNA is translated instantly. Thus, it does not need to enter the nucleus to be functional. Also, it does not integrate into the genome and therefore does not have the risk of insertional mutagenesis. Moreover, IVT mRNA is only transiently active and is completely degraded via physiological metabolic pathways. Due to these reasons, IVT mRNA has undergone extensive preclinical investigation.

=== Compound applications === Molybdenum disulfide (MoS2) is used as a solid lubricant and a high-pressure high-temperature (HPHT) anti-wear agent. It forms strong films on metallic surfaces and is a common additive to HPHT greases — in the event of a catastrophic grease failure, a thin layer of molybdenum prevents contact of the lubricated parts. When combined with small amounts of cobalt, MoS2 is also used as a catalyst in the hydrodesulfurization (HDS) of petroleum. In the presence of hydrogen, this catalyst facilitates the removal of nitrogen and especially sulfur from the feedstock, which otherwise would poison downstream catalysts. HDS is one of the largest scale applications of catalysis in industry. Molybdenum oxides are important catalysts for selective oxidation of organic compounds. The production of the commodity chemicals acrylonitrile and formaldehyde relies on MoOx-based catalysts. Molybdenum disilicide (MoSi2) is an electrically conducting ceramic with primary use in heating elements operating at temperatures above 1500 °C in air. Molybdenum trioxide (MoO3) is used as an adhesive between enamels and metals. Lead molybdate (wulfenite) co-precipitated with lead chromate and lead sulfate is a bright-orange pigment used with ceramics and plastics. The molybdenum-based mixed oxides are versatile catalysts in the chemical industry. Some examples are the catalysts for the oxidation of carbon monoxide, propylene to acrolein and acrylic acid, the ammoxidation of propylene to acrylonitrile.

Sources: en.wikipedia.org

Background from the literature

Benorterone, also known as 17α-methyl-B-nortestosterone or as 17α-methyl-B-norandrost-4-en-17β-ol-3-one, is a synthetic androstane steroid and a derivative of testosterone. Specifically, it is the C17α methyl and B-nor analogue of testosterone and the B-nor analogue of methyltestosterone. Other testosterone-derived steroidal antiandrogens include abiraterone acetate, BOMT, delanterone, dienogest, galeterone, metogest, mifepristone, oxendolone, rosterolone, topterone, trimethyltrienolone, and zanoterone, while progesterone-derived steroidal antiandrogens include examples like cyproterone and cyproterone acetate.

A decrease in total free energy was observed to be a result of the assembly of nanoparticles at an oil/water interface. When moving to the interface, particles reduce the unfavorable contact between the immiscible fluids and decrease the interfacial energy. The decrease in total free energy for microscopic particles is much larger than that of thermal energy, resulting in an effective confinement of large colloids to the interface. Nanoparticles are restricted to the interface by an energy reduction comparable to thermal energy. Thus, nanoparticles are easily displaced from the interface. A constant particle exchange then occurs at the interface at rates dependent on particle size. For the equilibrium state of assembly, the total gain in free energy is smaller for smaller particles. Thus, large nanoparticle assemblies are more stable. The size dependence allows nanoparticles to self-assemble at the interface to attain its equilibrium structure. Micrometer- size colloids, on the other hand, may be confined in a non-equilibrium state.

=== Development === In the course of his work on lysozyme, Chain read papers on the enzyme in the British Journal of Experimental Pathology by Alexander Fleming in volumes 3 and 8, and by Florey in volume 11. While doing so he came across Fleming's paper discussing the antibacterial effects of Penicillium notatum mould in volume 10. The erroneous impression given by Fleming that penicillin was a bactericidal enzyme led Chain to consider that it would be similar to lysozyme. Money was short at the time; the office had an overdraft of £500 (equivalent to £31,000 in 2025) and Florey had to forbid the purchase of any further equipment. Chain and Florey decided to create a large research project on antibacterial substances produced by micro-organisms that could attract long-term funding. Three sources were initially chosen for investigation: Bacillus subtilis, Trueperella pyogenes and penicillin mould. Florey later said:

The artist coined terms such as "PENtings" and "Media Graffiti" to describe his varied output. British artist James Mylne has been creating photo-realistic artwork using mostly black ballpoints, sometimes with minimal mixed-media color. The ballpoint pen has several limitations as an art medium. Color availability and sensitivity of ink to light are among concerns of ballpoint pen artists. As a tool that uses ink, marks made with a ballpoint pen can generally not be erased. Additionally, "blobbing" ink on the drawing surface and "skipping" ink-flow require consideration when drawing with a ballpoint pen. Although the mechanics of ballpoint pens remain relatively unchanged, ink composition has evolved to solve certain problems over the years, resulting in unpredictable sensitivity to light and some extent of fading.

Possibly the most common use of affinity chromatography is for the purification of recombinant proteins. Proteins with a known affinity are protein tagged in order to aid their purification. The protein may have been genetically modified so as to allow it to be selected for affinity binding; this is known as a fusion protein. Protein tags include hexahistidine (His), glutathione-S-transferase (GST), maltose binding protein (MBP), and the Colicin E7 variant CL7 tag. Histidine tags have an affinity for nickel, cobalt, zinc, copper and iron ions which have been immobilized by forming coordinate covalent bonds with a chelator incorporated in the stationary phase. For elution, an excess amount of a compound able to act as a metal ion ligand, such as imidazole, is used. GST has an affinity for glutathione which is commercially available immobilized as glutathione agarose. During elution, excess glutathione is used to displace the tagged protein. CL7 has an affinity and specificity for Immunity Protein 7 (Im7) which is commercially available immobilized as Im7 agarose resin. For elution, an active and site-specific protease is applied to the Im7 resin to release the tag-free protein.

Sources: en.wikipedia.org

Reference notes

=== On multi drug resistant cancer cells === Poloxamers have been shown to preferentially target cancer cells, due to differences in the membrane of these cells when compared to noncancer cells. Poloxamers have also been shown to inhibit MDR proteins and other drug efflux transporters on the surface of cancer cells; the MDR proteins are responsible for the efflux of drugs from the cells and hence increase the susceptibility of cancer cells to chemotherapeutic agents such as doxorubicin. Another effect of the polymers upon cancer cells is the inhibition of the production of ATP in multi-drug resistant (MDR) cancer cells. The polymers seem to inhibit respiratory proteins I and IV, and the effect on respiration seems to be selective for MDR cancer cells, which may be explained by the difference in fuel sources between MDR and sensitive cells (fatty acids and glucose respectively). The poloxamers have also been shown to enhance proto-apoptotic signaling, decrease anti-apoptoic defense in MDR cells, inhibit the glutathione/glutathione S-transferase detoxification system, induce the release of cytochrome C, increase reactive oxygen species in the cytoplasm, and abolish drug sequestering within cytoplasmic vesicles.

St. John's wort affects the clearance of numerous drugs, including cyclosporin, SSRI antidepressants, digoxin, indinavir, and phenprocoumon. It may also interact with the anti-cancer drugs irinotecan and imatinib. Salvia miltiorrhiza may enhance anticoagulation and bleeding among people taking warfarin. Allium sativum has been found to decrease the plasma concentration of saquinavir, and may cause hypoglycemia when taken with chlorpropamide. Ginkgo biloba can cause bleeding when combined with warfarin or aspirin. Concomitant Ephedra and caffeine use has been reported to, in rare cases, cause fatalities.

=== May === May 1 – Lubbock, Texas votes to become the largest city in U.S. to ban abortion with the "sanctuary city for the unborn". May 4 – COVID-19 pandemic – Michigan relaxes several restrictions regarding face mask requirements and outdoor gatherings. May 5 – South Carolina House votes to add firing squad to execution methods; South Carolina would become the fourth state to use firing squad after Mississippi, Oklahoma and Utah. May 7 Colonial Pipeline cyberattack: An oil pipeline in Houston is hacked by DarkSide causing the pipeline operator to shut down its entire network, the source of nearly half of the U.S. East Coast's fuel supply. COVID-19 vaccines – Pfizer/BioNTech seek full approval from the FDA for the Pfizer–BioNTech COVID-19 vaccine. May 9 – 2021 Colorado Springs shooting: Seven people are shot dead at a birthday party in Colorado Springs, Colorado. May 10 – COVID-19 vaccination: The FDA authorizes the Pfizer–BioNTech COVID-19 vaccine for adolescents aged 12–15 years old. May 11 – The Colonial Pipeline shutdown enters its fifth day. Panic buying by motorists causes many eastern seaboard gas stations to begin running dry. U.S. Energy Secretary Jennifer Granholm urges calm and to not hoard. May 12 Colonial Pipeline begins restarting, but warns that it will take several days for things to return to normal operations. COVID-19 vaccination – The Centers for Disease Control and Prevention (CDC) adopts the FDA recommendation to provide the Pfizer–BioNTech vaccine to adolescents aged 12–15 years old.

Tolkien was English, and thought of himself as such. His immediate paternal ancestors were middle-class craftsmen who made and sold clocks, watches and pianos in London and Birmingham. The Tolkien family originated in the East Prussian town of Kreuzburg near Königsberg, which had been founded during the medieval German eastward expansion, where his earliest-known paternal ancestor, Michel Tolkien, was born around 1620. In 1792 John Benjamin Tolkien and William Gravell took over the Erdley Norton manufacture in London, which from then on sold clocks and watches under the name Gravell & Tolkien. John Benjamin's brother Daniel Gottlieb Tolkien obtained British citizenship in 1794, but John Benjamin Tolkien apparently never became a British citizen. Other German relatives joined the two brothers in London. Several people with the surname Tolkien or similar spelling, some of them members of the same family as J. R. R. Tolkien, live in northern Germany, but most of them are descendants of people who were evacuated from East Prussia in 1945, at the end of the Second World War. According to Ryszard Derdziński, the surname Tolkien is of Low Prussian origin and probably means "son/descendant of Tolk". Tolkien mistakenly believed his surname derived from the German word tollkühn, meaning "foolhardy", and jokingly inserted himself as a "cameo" into The Notion Club Papers under the literally translated name Rashbold. However, Derdziński has demonstrated this to be a false etymology. Another suspected origin is the East Prussian village of Tołkiny. While J. R. R.

==== Suppression of Cossack autonomy in the Russian Empire ==== Historian Gary Dean Peterson writes: "With all this unrest, Ivan Mazepa of the Ukrainian Cossacks was looking for an opportunity to secure independence from Russia and Poland". In response to Mazepa's alliance with Charles XII of Sweden, Peter I ordered the sacking of the then capital of the Hetmanate, Baturyn. The city was burnt and looted, and 11,000 to 14,000 of its inhabitants were killed. The destruction of the Hetmanate's capital was a signal to Mazepa and the Hetmanate's inhabitants of severe punishment for disloyalty to the Tsar's authority. The Zaporizhian Sich at Chortomlyk, which had existed since 1652, was also destroyed by Peter I's forces in 1709, in retribution for decision of its otaman Kost Hordiyenko, to ally with Mazepa. Under Russian rule, the Cossack nation of the Zaporozhian Host was divided into two autonomous republics of the Russian Tsardom: the Cossack Hetmanate, and the more independent Zaporizhia. These organizations gradually lost their autonomy, and were abolished by Catherine II in the late 18th century. The Hetmanate became the governorship of Little Russia, and Zaporizhia was absorbed into New Russia.

Sources: en.wikipedia.org

Frequently asked questions

What is cardarine?

Cardarine is an investigational synthetic compound that acts as a PPARδ agonist. It is also known as GW501516 and has been studied mainly in preclinical research. It is not an approved medicine.

Is cardarine a steroid?

No. Cardarine is not a steroid hormone; it targets the nuclear receptor PPARδ. Its classification in anti-doping rules differs from anabolic steroids, though it remains prohibited in sport.

Why was cardarine not developed further?

Early rodent studies reported tumor formation at multiple sites, which raised safety concerns. Sponsors stopped clinical development, and no approved human product exists.

Is cardarine legal?

Legal status varies by country. It is not approved as a medicine, and it is prohibited in sport. Some jurisdictions restrict import, sale, or possession.

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