PPARδ agonist 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.
Updated 2025-11-21. Numbers and descriptions here follow the published literature rather than marketing material.
Clinical development stopped after rodent studies showed tumors at multiple sites. Whether those findings predict human cancer risk remains an open question, but they led sponsors to discontinue programs. Human safety data are limited to small, short-term studies that were not designed to assess cancer risk. Reported effects in those studies included changes in blood lipids, but the evidence is insufficient for medical use. Long-term consequences of nonmedical use are not well characterized. Questions about dose, duration, and individual susceptibility remain unresolved.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | GW501516; GW-1516; endurobol | GW501516 is the research code |
| Drug class | PPARδ agonist | Not a selective androgen receptor modulator |
| Molecular formula | C21H18F3NO3S2 | Established chemical formula |
| Molar mass | 453.5 g/mol | Calculated from the formula |
| Regulatory status | Prohibited in sport; not approved as medicine | Status varies by country |
Quality assessment for cardarine samples usually combines identity, purity, and impurity testing. Nuclear magnetic resonance spectroscopy and mass spectrometry can confirm molecular structure, while high-performance liquid chromatography estimates purity. Certificates of analysis from testing laboratories may list these results, but they do not establish safety or legality. In the absence of approved manufacturing, products sold online may contain the wrong compound, variable amounts, or unlisted contaminants. Independent verification is therefore central to analytical work and to interpreting any reported biological activity.
Laboratory detection of GW501516 commonly uses liquid chromatography coupled with tandem mass spectrometry. The method can identify the parent compound or its metabolites in urine and blood after sample cleanup. Protein precipitation, solid-phase extraction, or enzymatic hydrolysis may precede analysis, depending on the matrix. Reference standards are required for accurate quantification and confirmation. Because the compound is not approved, testing often occurs in anti-doping, forensic, or research settings rather than routine clinical care. Results are reported with limits of detection and quantification.
Stability of GW501516 depends on form, temperature, light exposure, and moisture. Solid reference material is typically stored frozen or refrigerated in a desiccator and protected from light. Solutions in organic solvents such as dimethyl sulfoxide are often kept frozen in aliquots to reduce freeze-thaw cycling. Aqueous solubility is low, so aqueous stock solutions can be difficult to prepare without cosolvents. Degradation may appear as changes in chromatographic purity or mass spectral signal. Stability studies are needed to establish shelf life for any specific preparation.
A common misconception is that cardarine has been proven safe for human use. In reality, human clinical data are limited, and long-term animal studies have raised concerns about cancer. Another misconception is that it is a supplement or vitamin-like compound. It is a synthetic research chemical with no approved medical indication. Scientific discussion often focuses on its mechanism and detection rather than therapeutic use. Regulatory and anti-doping literature treats it primarily as a prohibited substance.
Cardarine is explicitly prohibited by the World Anti-Doping Agency under the class of PPARδ agonists. Its presence in urine or blood samples can be detected using mass spectrometry-based methods, often liquid chromatography-tandem mass spectrometry. Athletes who test positive may face sanctions, including bans from competition. The compound is also regulated as a prescription-only or unapproved drug in many countries. Enforcement varies by jurisdiction, and some regions treat it as a controlled substance. Online sales may occur despite these restrictions, creating quality and legal risks.
Laboratory detection of cardarine typically involves sample preparation followed by chromatographic separation and mass spectrometric identification. Urine is the most common matrix for anti-doping tests, though blood and hair have also been explored. Methods can target the parent compound or its metabolites, depending on the expected window of detection. Reference standards are required for accurate quantification. Matrix effects and dilution can influence results, so laboratories use internal standards and validation protocols. The exact detection window varies with dose, route, and individual metabolism.
A persistent misconception is that cardarine is a fat-burning drug or a safe alternative to anabolic steroids. No approved therapeutic product exists, and human safety data are limited. The tumor findings in rodents remain a central concern in scientific reviews. Products sold online may contain inaccurate labels, impurities, or different compounds entirely, which complicates any assessment of effects. Independent testing of such products has reported frequent mislabeling. For these reasons, discussions in the literature emphasize risks and unknowns rather than benefits.
Cardarine is not approved for human therapeutic use in any major jurisdiction. It appears on the World Anti-Doping Agency Prohibited List as a PPARδ agonist within the hormone and metabolic modulators category. Sports organizations test for it because it has been detected in athlete samples and seized products. Regulatory actions against marketed research chemical versions have occurred in several countries, though enforcement varies. Availability through unregulated channels complicates oversight.
Analytical laboratories typically identify cardarine and its metabolites using liquid chromatography-tandem mass spectrometry. Urine is a common matrix in anti-doping testing, while blood and tissue may be used in research settings. Detection windows depend on the assay, the sample matrix, and the compound's metabolism. Because cardarine is extensively metabolized, laboratories often target specific metabolites to improve sensitivity and confirmation. Reference standards are required for reliable quantification. Method validation includes checks for selectivity, linearity, and carryover.
== Function == Membrane-Bound RAGE (mRAGE): mRAGE acts as a cellular receptor capable of activating inflammatory and oxidative stress pathways in response to ligand binding. The receptor's structure, which includes the ligand-binding domain, transmembrane segment, and cytoplasmic tail, is critical for these functions. The wide variety of ligands that interact with mRAGE contributes to its involvement in multiple pathological states, such as diabetes, neurodegeneration, and cardiovascular diseases. Soluble RAGE (sRAGE): On the other hand, sRAGE functions as a decoy receptor. It circulates in the bloodstream and binds RAGE ligands, thereby preventing them from activating mRAGE on the cell surface. By neutralizing these ligands, sRAGE reduces RAGE-mediated cellular activation and inflammation. Elevated levels of sRAGE are considered to have a protective effect in inflammatory diseases by limiting the activity of harmful ligands. The balance between mRAGE and sRAGE levels is thought to influence disease outcomes. An excess of mRAGE is often associated with inflammation and disease progression, whereas higher concentrations of sRAGE may be beneficial in mitigating inflammatory responses.
CEP-32496 (renamed RXDX-105) a small molecule inhibitor of BRAF, EGFR and RET, now in Phase I/II trials CEP-40783 (renamed RXDX-106) a small molecule inhibitor of AXL and c-Met in preclinical development CEP-40125 (renamed RXDX-107) a nanoformulation of a modified bendamustine with potential activity in solid tumours. Bendamustine Rapid Infusion as therapy for CLL and NHL is part of Teva's specialty drugs pipeline. TEV-44229 (renamed RXDX-108) a potent inhibitor of the kinase PKCiota In July 2019, the company stopped production of Vincristine, a critical drug used to treat the most common forms of childhood cancer, and was criticized by media for creating a worldwide shortage of the drug. On 28 January 2020, the company announced that the Food and Drug Administration (FDA) had approved an autoinjector device for Ajovy (fremanezumab-vfrm) injection.
== Preparation == The compound is prepared by reacting 4-tert-butylbenzoic methyl ester (from 4-tert-butylbenzoic acid by esterification with methanol) with 4-methoxyacetophenone in toluene in the presence of sodium amide via Claisen condensation.
==== Sublabial ==== Sublabial administration is achieved by placing the drug between the lip and gum. The frenulum of the tongue may be irritated when in contact with corrosive materials but can be avoided with this route. It is usually used for medications such as nitroglycerin, for example.
It has also been linked to the production of RNA-edited proteins that are incorporated into the polypeptide complexes of the respiration pathway. Therefore, it is highly probable that polypeptides synthesized from unedited RNAs would not function properly and hinder the activity of both mitochondria and plastids. C-to-U RNA editing can create start and stop codons, but it cannot destroy existing start and stop codons. A cryptic start codon is created when the codon ACG is edited to be AUG.
Sources: en.wikipedia.org
Dirt spawned five singles that reached the top 30 on the Billboard Mainstream Rock chart: "Would?", "Rooster", "Them Bones", "Angry Chair", and "Down in a Hole", and remained on the charts for nearly two years. Alice in Chains was added as openers to Ozzy Osbourne's No More Tours tour. Days before the tour began, Layne Staley broke his foot in an ATV accident, forcing him to use crutches on stage. Starr left the band after the release of Dirt. Staley told Rolling Stone in 1994 about Starr leaving the band, "It was just a difference in priorities. We wanted to continue intense touring and press. Mike was ready to go home." Years later, Starr claimed that he was fired due to his drug addiction. Starr was replaced by former Ozzy Osbourne bassist Mike Inez. Inez had met Alice in Chains during Ozzy Osbourne's No More Tours tour and became friends with them. When the band was in Brazil, they called Inez to join them and he accepted. Inez wanted to do the shows in Brazil and even got his immunization shots, but the band called him back saying that Starr wanted to do the last two shows in Brazil, so they would meet Inez in London instead. Inez ended up getting sick with his vaccination shots for a couple of days. Inez played his first concert with Alice in Chains on January 27, 1993, at the Camden Underworld in London. In April 1993, the band recorded two songs with Inez, "What the Hell Have I" and "A Little Bitter", for the Last Action Hero soundtrack.
After the Colombian government dismantled many of the drug cartels that appeared in the country during the 1980s, left-wing guerrilla groups, and right-wing paramilitary organizations resumed some of their drug trafficking activities. They resorted to extortion and kidnapping for their financing: activities which led to a loss of support from the local population. These funds helped finance paramilitaries and guerrillas, allowing these organizations to buy weapons which were then sometimes used to attack military and civilian targets. Natural resources were found to be correlated with the conflict, while higher per capita income and public investment were associated with reduced conflict intensity. During the presidency of Álvaro Uribe, the government applied more military pressure on the FARC and other outlawed far-left groups. After the offensive, many security indicators improved. As part of a controversial peace process, the AUC (a right-wing paramilitary group) as a formal organization had ceased to function. Colombia achieved a considerable reduction in cocaine production, leading White House drug czar R. Gil Kerlikowske to announce that Colombia was no longer the world's biggest producer of cocaine. In February 2008, millions of Colombians demonstrated against the FARC and other outlawed groups. The Colombian Ministry of Defense reported 19,504 deserters from the FARC between August 2002 and their collective demobilization in 2017, peaking in the year 2008. During these years, the military forces of the Republic of Colombia were strengthened.
== Function and pathology == Lp(a) is assembled at the hepatocyte cell membrane surface, which is similar to typical LDL particles. However, there are other possible locations of assembly. The particles mainly exist in plasma. Lp(a) contributes to the process of atherogenesis. The structure of apolipoprotein(a) is similar to plasminogen and tPA (tissue plasminogen activator), and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Also, because Lp(a) stimulates secretion of PAI-1, it leads to thrombogenesis. It also may enhance coagulation by inhibiting the function of tissue factor pathway inhibitor. Moreover, Lp(a) carries atherosclerosis-causing cholesterol and binds atherogenic pro-inflammatory oxidised phospholipids as a preferential carrier of oxidised phospholipids in human plasma, which attracts inflammatory cells to vessel walls and leads to smooth muscle cell proliferation. Moreover, Lp(a) also is hypothesised to be involved in wound healing and tissue repair by interacting with components of the vascular wall and extracellular matrix. Apo(a), a distinct feature of the Lp(a) particle, binds to immobilized fibronectin and endows Lp(a) with the serine-proteinase-type proteolytic activity. Nonetheless, individuals without Lp(a) or with very low Lp(a) levels seem to be healthy. Thus, plasma Lp(a) is not vital, at least under normal environmental conditions.
== Measuring peak separation == There are several ways to define the minimum peak separation ΔM in mass spectrometry, therefore it is important to report the method used to determine mass resolution when reporting its value. The two most widely used are the peak width definition and the valley definition.
=== Elastocaloric refrigeration === Another potential solid-state refrigeration technique and a relatively new area of study comes from a special property of super elastic materials. These materials undergo a temperature change when experiencing an applied mechanical stress (called the elastocaloric effect). Since super elastic materials deform reversibly at high strains, the material experiences a flattened elastic region in its stress-strain curve caused by a resulting phase transformation from an austenitic to a martensitic crystal phase. When a super elastic material experiences a stress in the austenitic phase, it undergoes an exothermic phase transformation to the martensitic phase, which causes the material to heat up. Removing the stress reverses the process, restores the material to its austenitic phase, and absorbs heat from the surroundings cooling down the material. The most appealing part of this research is how potentially energy efficient and environmentally friendly this cooling technology is. The different materials used, commonly shape-memory alloys, provide a non-toxic source of emission free refrigeration. The most commonly studied materials studied are shape-memory alloys, like nitinol and Cu-Zn-Al. Nitinol is of the more promising alloys with output heat at about 66 J/cm3 and a temperature change of about 16–20 K. Due to the difficulty in manufacturing some of the shape memory alloys, alternative materials like natural rubber have been studied.
Sources: en.wikipedia.org
No. Cardarine is GW501516, a PPARδ agonist, while SARMs act on androgen receptors. The two classes are often grouped in informal discussions despite different mechanisms.
No. It has no approved medical indication in any country. Regulatory agencies have not cleared it for treatment or prevention of any condition.
Early clinical work stopped after rodent carcinogenicity findings. Those animal results raised concerns about long-term human risk, although direct human evidence is lacking. The human relevance of the tumors remains an open scientific question.
It targets PPARδ, a nuclear receptor involved in lipid and energy metabolism. It does not act primarily on androgen receptors. This distinction separates it from SARMs.