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Cardarine As Investigational Pparδ Agonist — Evidence Review

By Editorial Desk · published 2025-08-27 · last reviewed 2025-10-16 · Data

LC-MS/MS is one of those subjects where the details matter more than the headlines. This page pulls together the background, the mechanisms, and the practical points readers ask about most.

Last reviewed on 2025-10-16. Where a claim depends on a specific study, the study is described rather than over-claimed.

Cardarine as Investigational PPARδ Agonist

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.

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.

Identity and Pharmacological Mechanism

The compound is typically described as a laboratory compound rather than a therapeutic product. Published reports have explored its role in lipid disorders, insulin sensitivity, and exercise metabolism, yet no major drug regulator has approved it for medical use. Commercial samples sold under the cardarine name may vary in purity and identity. Analytical confirmation is therefore necessary when the material is discussed in scientific or regulatory contexts. Its classification as a prohibited substance in sport further shapes how it is studied and reported.

Cardarine is a common name for GW501516, a synthetic compound studied for its effects on lipid and glucose metabolism. It functions as an agonist at peroxisome proliferator-activated receptor delta, or PPARδ, a nuclear receptor that influences gene expression. The molecule is not a steroid, nor is it a selective androgen receptor modulator. It is also known in research and sports literature as GW-501516 and endurobol. Early laboratory work examined its metabolic activity in cell cultures and animal models.

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.

Mechanism and Detection

Preclinical research reported that GW501516 increased running endurance in mice and improved lipid profiles in some animal species. Early human trials explored effects on high-density lipoprotein cholesterol, triglycerides, and glucose handling, but the program was discontinued. Published human data are sparse and do not establish efficacy for any condition. Studies also examined PPAR delta in cancer biology, with conflicting findings across models. The relationship between receptor activation, tissue context, and disease risk remains an active area of investigation.

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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Identity and Regulatory Status

Cardarine is a common name for GW501516, an investigational compound developed in the 1990s for metabolic conditions. It acts as an agonist at peroxisome proliferator-activated receptor delta, a nuclear receptor involved in lipid and energy metabolism. The compound is frequently mislabeled as a selective androgen receptor modulator, or SARM, but its molecular target is different. GW501516 reached early clinical testing before development was discontinued. It has no approved therapeutic use in any country. The name cardarine is not a formal international nonproprietary name.

Regulatory treatment varies, but cardarine is not approved as a medicine. Sports authorities list GW501516 as a prohibited substance, and it is banned at all times under the World Anti-Doping Agency code. Many countries restrict sales for human consumption, while online vendors market it as a research chemical. Such products may lack purity data, and their actual contents can differ from the label. Purchasing or possessing cardarine may carry legal consequences depending on jurisdiction. The compound is not a dietary supplement ingredient in regulated markets.

Regulation and Detection

Cardarine has no approved therapeutic indication and is not marketed as a medicine. The World Anti-Doping Agency lists GW501516 as a prohibited substance at all times, covering both in-competition and out-of-competition periods. National laws vary: some countries treat it as an unapproved drug subject to import controls, while others have specific restrictions on sale for human consumption. It is often sold as a research chemical, a label that does not imply safety or legality. Enforcement actions have targeted online vendors and shipments.

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.

Mechanism and Safety Research

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.

Early clinical research explored GW501516 for lipid disorders, obesity, and diabetes. Some short-term human studies reported changes in HDL cholesterol, LDL cholesterol, and triglycerides. The development program was discontinued after rodent studies showed dose-dependent tumor formation in multiple tissues, including liver, bladder, stomach, and skin. These findings raised concerns about long-term cancer risk in humans. Because human exposure data are limited, the clinical significance of the rodent tumors remains uncertain.

Reference notes

== Toxicity == Toxicity data in humans are limited, although laboratory studies indicate that certain compounds in the bark and roots or their extracts may cause adverse effects when consumed in excess. Supplementation with M. oleifera leaf extract is potentially toxic at levels exceeding 3,000 mg/kg of body weight, but safe at levels below 1,000 mg/kg. A study on albino mice found that high levels (>5,000mg/kg) of consumption could impair renal function. M. oleifera may interfere with prescription drugs affecting cytochrome P450 (including CYP3A4) and may inhibit the antihyperglycemic effect of sitagliptin. In November 2025, Food Standards Australia New Zealand (FSANZ) rejected an application to approve Moringa oleifera leaves, immature pods, and oil as a novel food. The decision cited insufficient evidence to confirm its safety for human consumption as a food. As a result (confirmed in May 2026 via Department of Agriculture notices), Moringa is not permitted as food or a food ingredient for retail sale in Australia.

==== Still-Gennari alkenation ==== The Horner-Wadsworth-Emmons reaction is a widely used olefination reaction in which a phosphonate-stabilized carbanion reacts with an aldehyde or ketone to form an alkene. In the standard HWE reaction, the phosphonate ester contains alkoxy substituents (typically methoxy or ethoxy), producing an E-alkene as the major product. In 1983, Still and Gennari reported that simply substituting the more electron-withdrawing 2,2,2-trifluoroethoxy groups on the phosphonate component reversed the stereoselectivity to produce predominantly Z-alkenes. The use of a non-coordinating counterion was also found to be critical for high levels of Z-selectivity; this is typically accomplished by using a base with a potassium counterion in the presence of 18-crown-6. Taken together, this protocol is known as the Still-Gennari modification of the Horner-Wadsworth-Emmons reaction or, alternatively, as the Still-Gennari olefination.

Dr. Gian Parkash Gopal. Founder, Oxford Hindu Temple and Community Centre Project. For services to the Hindu Community and to Multi-Faith Cohesion in Oxfordshire. Elizabeth Jane Gorb. Director of Apprenticeships, Manchester Metropolitan University. For services to Education and Skills. Permjit Gosal (Pam Gosal), MSP. Member of the Scottish Parliament for West Scotland. For services to Business, to Racial Equality and to Charity in Milton Keynes. David James Connelly Graham. National Director, Care Leavers Association. For services to Care Leavers. Sarah Jane Vandevelde Graham. Founder, Hilltops Ukrainian Support Community. For services to Ukrainian Refugees. The Reverend Canon Terence Kevin Declan Graham, DL. Rector, St Bartholomew's Church, Belfast. For services to the Reserve Forces and to the community in Belfast. Julie Grant. Deputy Director, News and Digital, Scottish Government. For services to Scotland on the Demise of Her Majesty Queen Elizabeth II. Dr. Simon Jonathon Grant. Technical Director, Thomas Swan. For services to Diversity in the Chemical Industry. Belinda Elizabeth Gray. Founder, Art for Cure. For services to Breast Cancer Charities. Julie Heather Gray. Founder, Adventure Activities for All Abilities. For services to Children with Impairments in Nottinghamshire. Neil Jonathan Greenwood. Executive Director, Finance and Corporate Services, Natural History Museum. For services to Museums. Robert Terence Grey. Lately Boxing Gym Owner and Trainer, Gwent Amateur Boxing Club. For services to Amateur Boxing in Swansea. Dr. John Michael Grimshaw.

In physics and chemistry, binding energy is the smallest amount of energy required to remove a particle from a system of particles or to disassemble a system of particles into individual parts. In the former meaning the term is predominantly used in condensed matter physics, atomic physics, and chemistry, whereas in nuclear physics the term separation energy is used. A bound system is typically at a lower energy level than its unbound constituents. According to relativity theory, a ΔE decrease in the total energy of a system is accompanied by a decrease Δm in the total mass, where Δmc2 = ΔE.

BRD-6929, also widely known as "compound 60" (Cpd-60 or Cmpd60), is a histone deacetylase (HDAC) inhibitor which is used in scientific research. It has been described in the past as the prototypical selective HDAC1 and HDAC2 inhibitor. However, subsequent findings suggest that BRD-6929 may not actually be selective for HDAC1 and HDAC2 over HDAC3.

Sources: en.wikipedia.org

Reference notes

=== August === 1 August: The second Donald Trump administration raises tariffs on New Zealand exports to the United States to 15 percent. Visual effects company Wētā FX proposes laying off 100 jobs in its support departments based in Wellington. 4 August: The New Zealand Government announces plans to scrap the National Certificate of Educational Achievement (NCEA) secondary school qualification. A name suppression order lapses for former Deputy Commissioner of Police Jevon McSkimming, who was charged in June 2025 with eight counts of possessing objectionable material including child sexual exploitation and bestiality over a four-year period. 5–6 August — An RNZAF C-130J Hercules evacuated three personnel of the United States National Science Foundation from McMurdo Station. 6 August: The Christchurch-based wool factory Wild Earth Yarns acquires the woollen dye house and spinning mill of the liquidated Napier-based company Design Spun. Hato Hone St John proposes scrapping various community voluntary programmes including hospital volunteers, community carers and pet therapy services as part of a review of its services; affecting about 1,100 people. 8 August – The Japanese Navy makes a stop-over in Wellington for the first time since 1936. 9–10 August – Prime Minister Luxon hosts Australian Prime Minister Anthony Albanese in Queenstown for annual bilateral head of government talks. 10 August — Gloriavale Christian Community's Overseeing Shepherd Howard Temple resigns after pleading guilty to 12 charges of sexual offending against women and girls last month.

=== Method Development === Method development of chiral chromatography is still done by screening of columns from the various classes of chiral columns. While chiral separation mechanisms are understandable in certain scenarios, and the retention characteristics of analytes within the chromatographic columns can occasionally be elucidated, the precise combination of chiral stationary phases (CSPs) and mobile-phase compositions that required to effectively resolve a specific enantiomeric pair often remains elusive. The chemistry of CSP ligands significantly influences the creation of in-situ diastereomeric complexes upon the stationary phase surface. However, other method's conditions, such as mobile-phase solvents, their composition, mobile phase additives and column temperature can play equally critical roles. The final resolution of the enantiomers is the outcome of combination of intermolecular forces, and even a subtle change in them can determine the success or failure of separation. This complexity prevents from establishing routine method-development protocols that are universally applicable to a diverse range of enantiomers. In fact, sometimes the outcome of previous unsuccessful experiments do not provide any clue for the subsequent steps.

In general, the A (aminoacyl) site contains an aminoacyl-tRNA (a tRNA esterified to an amino acid on the 3' end). The P (peptidyl) site contains a tRNA esterified to the nascent peptide. The free amino (NH2) group of the A site tRNA attacks the ester linkage of P site tRNA, causing transfer of the nascent peptide to the amino acid in the A site. This reaction is takes place in the peptidyl transferase center The E (exit) site contains a tRNA that has been discharged, with a free 3' end (with no amino acid or nascent peptide). A single mRNA can be translated simultaneously by multiple ribosomes. This is called a polysome. In prokaryotes, much work has been done to further identify the importance of rRNA in translation of mRNA. For example, it has been found that the A site consists primarily of 16S rRNA. Apart from various protein elements that interact with tRNA at this site, it is hypothesized that if these proteins were removed without altering ribosomal structure, the site would continue to function normally. In the P site, through the observation of crystal structures it has been shown the 3' end of 16s rRNA can fold into the site as if a molecule of mRNA. This results in intermolecular interactions that stabilize the subunits. Similarly, like the A site, the P site primarily contains rRNA with few proteins. The peptidyl transferase center, for example, is formed by nucleotides from the 23S rRNA subunit. In fact, studies have shown that the peptidyl transferase center contains no proteins, and is entirely initiated by the presence of rRNA.

The technology has wide application, in environmental testing laboratories, life science and food companies, chemical/petrochemical firms, power generation facilities, electronics manufacturers, government agencies, and academic institutions. For example, during semiconductor production, Dionex instruments are used to detect and prevent ionic contamination, which can cause degradation of semiconductor surfaces and deterioration of their electrical properties. The Environmental Protection Agency has approved instruments such as the Dionex AS4 column for the analysis of anions in drinking water. Dionex columns are used by municipalities seeking to ensure the safety of drinking water and by companies selling bottled waters. The company made a point of developing worldwide distribution channels: as of 2007 Dionex's sales were distributed relatively evenly between North America, Europe, and the Asia/Pacific area. In the area of ion chromatography (IC), Dionex controlled more than 70 percent of a $200 million worldwide market. In the newer area of high-performance liquid chromatography (HPLC), which Dionex entered in 1998, the company held a much smaller place (1%) in a much larger market ($2 billion market). Bowman directed the company from its early stages of development, as a small branch of a larger company with approximately $1 million in revenues in a year, to its position as publicly traded enterprise with an established international revenue stream in the hundreds of millions of dollars. Bowman retired as president and chief executive officer of Dionex in 2002.

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.

What is cardarine?

Cardarine is a common name for GW501516, a synthetic PPARδ agonist. It is not a steroid or a selective androgen receptor modulator. It was developed and studied as a research compound for metabolic pathways.

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