If you have been reading about nuclear receptor and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-07-19. Where a claim depends on a specific study, the study is described rather than over-claimed.
Safety concerns emerged from long-term animal studies. In rodents given the compound for extended periods, researchers found an increased incidence of certain cancers, including liver and bladder tumors. These findings contributed to the discontinuation of clinical development. Whether similar risks apply to short-term or low-level exposure in humans is not established, and controlled human safety data are limited. The relevance of high-dose rodent carcinogenicity findings to human use remains a subject of debate.
Human trials of GW501516 were small and short in duration. They examined lipid levels, glucose handling, and other metabolic markers, but the programs were halted after the animal cancer findings. No approved therapeutic product exists, and published human data are insufficient for establishing long-term safety. Reports of use for athletic performance come mainly from non-clinical settings and cannot be verified through controlled trials. Independent testing of products sold as cardarine has found inconsistent purity and labeling.
Laboratory studies indicate that GW501516 activates PPARδ, a nuclear receptor involved in fatty acid oxidation and energy metabolism. In rodent experiments, treated animals often showed increased endurance and reduced fat mass. These effects were observed under controlled conditions and do not establish safe or effective use in humans. The exact dose-response relationship in humans remains poorly characterized. Species differences in metabolism can affect how results translate across animals and people.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Primary target | PPARδ (NR1C2) | Nuclear receptor involved in lipid metabolism |
| Preclinical effect | Increased fatty acid oxidation | Observed in rodent studies |
| Key safety signal | Tumors in rodents after long-term exposure | Contributed to halted clinical development |
| Human trial status | No approved product; development stopped | Limited short-term metabolic data |
| Sport regulatory status | Prohibited at all times | WADA hormone and metabolic modulators class |
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 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.
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.
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 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.
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.
GW501516 acts as a selective agonist at PPARδ, a nuclear receptor that regulates transcription of genes involved in lipid handling and energy metabolism. Activation of PPARδ in preclinical models increases fatty acid oxidation, mitochondrial biogenesis, and exercise endurance in rodents. These effects have made the compound a subject of metabolic research and also a target for sport anti-doping rules. In humans, however, controlled studies are limited, and whether similar endurance or metabolic changes occur at tolerated exposures remains an open question. The receptor’s broad tissue distribution also means downstream effects may vary by organ and condition.
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.
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to IFN, this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (IRF9) and form ISGF-3 (IFN-stimulated gene factor-3), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. ISGF-3 proceeds the activation of genes via the IFN-stimulated response element (ISRE). ISRE-driven genes include Ly-6C, the double-stranded RNA kinase (PKR), 2´ to 5´ oligoadenylate synthase (OAS), MX and potentially MHC class I. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus. STAT2 knockout mice are unresponsive to type I IFN and extremely vulnerable to viral infection. They indicate the loss of the type I IFN autocrine loop and several defects in macrophages and T cell responses. Stat2-/- cells show differences in the biological response to IFN-α.
Albert Lester Lehninger (February 17, 1917 – March 4, 1986) was an American chemist in the field of bioenergetics. He made fundamental contributions to the current understanding of metabolism at a molecular level. In 1948, he discovered, with Eugene P. Kennedy, that mitochondria are the site of oxidative phosphorylation in eukaryotes, which ushered in the modern study of energy transduction. He is the author of a number of classic texts, including Biochemistry, The Mitochondrion, Bioenergetics and, most notably, his series Principles of Biochemistry. This last is a widely used text for introductory biochemistry courses at the college and university levels. Lehninger was born in Bridgeport, Connecticut, US. He earned his BA in English from Wesleyan University (1939) and went on to earn both his MA (1940) and PhD (1942) at the University of Wisconsin–Madison. His doctoral research involved the metabolism of acetoacetate and fatty acid oxidation by liver cells.
In the phosphatidylinositol signal pathway, the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes PIP2 into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca2+ channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses. The effects of Ca2+ are also remarkable: it cooperates with DAG in activating PKC and can activate the CaM kinase pathway, in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca2+-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
Sources: en.wikipedia.org
Alfred Ellis Wilhelmi (1910–1994) was an American endocrinologist recognized for contributing to the understanding of anterior pituitary hormones. Born in Lakewood, Ohio, Wilhelmi attended Cleveland public schools. Wilhelmi earned a B.S. degree in premedical sciences from Western Reserve University in 1933. He then attended Oxford University as a Rhodes Scholar, where he obtained a B.A. in 1933 and Ph.D. in animal physiology in 1937. He then joined Yale University's Biochemistry Department, rising to the position of Professor in 1950. Wilhelmi chaired the Department of Biochemistry at Emory University School of Medicine from 1950 to 1977. In 1960, he was named Charles Howard Candler Professor of Biochemistry. In 1979, he received Emory's Thomas Jefferson award for service to the university and community. Wilhelmi also was President of the Endocrine Society from 1968 to 1969. During his career, he published over 80 articles in scientific journals.
The ISOLDE facility contains the Class A laboratories, buildings for the HIE-ISOLDE and MEDICIS projects, and the control rooms located in building 508. Before ISOLDE, the radioactive nuclides were transported from the production are to the laboratory for examination. At ISOLDE, all processes from the production to the measurements are connected and the radioactive material requires no extra transport. Due to this, ISOLDE is referred to as an on-line facility. At the ISOLDE facility, the main proton beam for reactions comes from the PSB. The incoming proton beam has an energy of 1.4 GeV and its average intensity varies up to 2 μA. The beam enters the facility and is directed towards one of two mass separators: the General Purpose Separator (GPS) and the High Resolution Separator (HRS). The separators have independently run target-ion source systems, delivering 60 keV RIBs.
There are several other bioprinting techniques which are less commonly used. Droplet-based bioprinting is a technique in which the bioink blend of cells and/or hydrogels are placed in droplets in precise positions. Most common amongst this approach are thermal and piezoelectric-drop-on-demand techniques. This method of bioprinting is often used experimentally with lung and ovarian cancer models. Thermal technologies use short duration signals to heat the bioink, inducing the formation of small bubbles which are ejected. Piezoelectric bioprinting has short duration current applied to a piezoelectric actuator, which induces a mechanical vibration capable of ejecting a small globule of bioink through the nozzle. A significant aspect of the study of droplet-based approaches to bioprinting is accounting for mechanical and thermal stress cells within the bioink experience near the nozzle-tip as they are extruded.
SPATT was introduced in 2004 as a method of monitoring aquatic toxins. This tool is able to adsorb toxins generated by microalgae or cyanobacteria, known as cyanotoxins. The adsorption is passive, and the biotoxins adhere to porous, resin filled sachets, or SPATT bags where they are then physically removed and examined. SPATT is a useful tool in tracking algal blooms as it is reliable, sensitive, and inexpensive. It has the ability to quickly alert the existence of aquatic toxins which prevents it from bioaccumulating in marine life. One of the downsides is that it does not give very good results for water-soluble toxins as compared to hydrophobic compounds. This tool is mainly used to determine intercellular concentrations of toxins but the cyanobacteria can also be lysed to determine the total toxin amount in a sample. Other drawbacks, such as a lack in calibration and the ability to only monitor dissolved toxins, make it difficult for this tool to be implemented in a more widespread manner. However, SPATT devices are able to detect many lipophilic and hydrophilic toxins that are linked to harmful algal bloom.
Sources: en.wikipedia.org
Rodent studies reported increased endurance and fat oxidation after GW501516 exposure. Long-term studies also found higher rates of some tumors, which led to halted development.
Small short-term human trials examined metabolic markers such as lipids and glucose. The trials did not continue after rodent cancer findings, so long-term human safety is unknown.
Controlled human trials have not established a performance benefit. Anecdotal reports exist, but they are not reliable evidence.
It binds to and activates PPAR delta, a nuclear receptor that controls expression of genes related to fatty acid oxidation. This mechanism can alter energy metabolism in animal models. It is not a direct stimulant or fat-burning enzyme.