The short version of nuclear receptor fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-12-22. Anything still debated is marked as such rather than presented as settled.
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 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 |
|---|---|---|
| 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 |
Activation of PPARδ changes transcription of genes involved in fatty acid transport, mitochondrial function, and skeletal muscle fuel preference. In rodent studies, pharmacological PPARδ activation was associated with increased endurance and altered body composition. These findings generated interest in performance enhancement, but species differences and study designs limit direct extrapolation to humans. Small human trials were conducted in the 2000s and later discontinued. The extent to which cardarine produces similar metabolic or performance effects in people remains an open question.
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 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.
Cardarine can be detected in biological samples and product materials using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method separates compounds by chromatography and identifies them by mass-to-charge transitions, allowing low-level detection in urine or blood. Sample preparation often involves enzymatic hydrolysis, solid-phase extraction, or protein precipitation. Certified reference materials and isotope-labeled internal standards improve quantification. Detection windows depend on metabolism, matrix, and assay sensitivity, so no single universal window applies.
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.
She was active in that role for over ten years. During that time she was also elected into the Association of American Physicians. In 2015 Dr. Huttenlocher was inducted as a Member of the National Academy of Medicine "for her pioneering studies of cell migration and alterations of cell migration in human diseases." In 2017, Huttenlocher was awarded a UW2020 grant to support her project "Engineering leukocytes generated from human iPS cells to treat human disease." At the same time, she was also elected a Fellow of the American Society for Cell Biology. In May 2020, Huttenlocher was named the Anna Ruth Brummett Professor of Pediatrics and Medical Microbiology and Immunology Chair in honor of her "major contributions to the advancement of knowledge." The following year, she was part of a large team of researchers from the University of Wisconsin Carbone Cancer Center recognized with the Society for the Immunotherapy of Cancer’s Team Science Award for "long-standing contribution to the field of cancer immunotherapy over the past 35 years." Huttenlocher's recent research projects include "Cell migration and wound repair" and "Imaging immunometabolism in live animals during host defense." In 2023, Huttenlocher published the book "From Loss to Memory: Behind the Discovery of Synaptic Pruning". It describes the discovery of synaptic pruning and its current relevance to early learning, autism, schizophrenia and Alzheimer's disease.
Unlike standard supply-chain management practices world-wide, some major concepts are not supported in the military domain. For example, the "just-in-time" (JIT) model emphasizes holding less (or no) inventory, whereas in military supply chains, due to the high costs of a stock-out (potentially placing lives in danger), keeping huge inventory is a more acceptable practice. Some examples of these are the ammunition dump and oil depot. Likewise, the military procurement process has much different criteria than the normal business procurement process. Military needs call for reliability of supply during both peace and war, as compared to price and technological factors.
In baboon skeletal muscle, which consists of fully differentiated postmitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage does not increase with age. Thus, telomere shortening does not appear to be a major factor in the aging of the differentiated cells of brain or skeletal muscle. In human liver, cholangiocytes and hepatocytes show no age-related telomere shortening. Another study found little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities. Some experiments have raised questions on whether telomerase can be used as an anti-aging therapy, namely, the fact that mice with elevated levels of telomerase have higher cancer incidence and hence do not live longer. On the other hand, one study showed that activating telomerase in cancer-resistant mice by overexpressing its catalytic subunit extended lifespan. A study found that long-lived subjects inherited a hyperactive version of telomerase. A telomerase activator TA-65 is commercially available and is claimed to delay aging and to provide relief from certain disease conditions. This formulation contains a molecule called cycloastragenol derived from a legume Astragalus membranaceus. Several other compounds have been found to increase telomerase activity: Centella asiatica extract 8.8-fold, oleanolic acid 5.9-fold, astragalus extract 4.3-fold, TA-65 2.2-fold, and maslinic acid 2-fold.
Sources: en.wikipedia.org
=== Cushing's Disease === Corticotropic cells can have detrimental effects on the body if they express too much or too little ACTH. One such example is Cushing's disease, which can result from overproduction of ACTH in the corticotropes due to pituitary tumors known as corticotroph adenomas; this is the cause for roughly two-thirds of those diagnosed with Cushing's disease. It is also possible that this disease can result from production of ACTH in a non-pituitary tumor, known as ectopic production, or the adrenal glands can overproduce cortisol due to an adrenal tumor. This overproduction of ACTH causes an increase in cortisol levels due to increased glucocorticoid synthesis in the adrenal cortex resulting in several associated symptoms. Symptoms of Cushing's disease include:
=== Major depressive disorder === The mechanistic rationale for KOR antagonism in major depressive disorder (MDD) derives from the observation that chronic stress and depression are associated with higher activity of the KOR system. KOR activation suppresses dopamine release and prevents dopamine rebound after stress exposure, thereby leading to anhedonia and depressive phenotypes. KOR antagonists reverse this pathway by disinhibiting dopaminergic tone and restoring reward sensitivity. KOR-mediated upregulation of pro-inflammatory signaling in microglia likely drives the depression pathophysiology, and antagonism may provide benefits. The claustrum-prelimbic cortex circuit operates via dynorphin and KOR signaling to modulate cognitive and affective functions. Buprenorphine/samidorphan (ALKS-5461) displayed antidepressant efficacy in randomized controlled trials as an adjunctive therapy and has shown durable effects with a favorable safety profile including low abuse potential and minimal withdrawal symptoms. A phase 2 study demonstrated significant reduction of depressive symptoms and improvement in anhedonia when aticaprant was added to existing antidepressant therapy. A phase 3 clinical trials (KOASTAL-1 and additional studies) of navacaprant failed to achieve statistically significant superiority over placebo across the broader MDD population, with its development discontinued for this purpose in early 2025.
== History == Nalfurafine was derived from structural modification of the opioid antagonist naltrexone. It was first synthesized and characterized in 1998, and was approved for clinical use in Japan as an intravenous drug under the brand name Remitch in 2009. The developer of nalfurafine also sought approval in Europe under the brand name Winfuran, but the marketing authorisation application was declined by the European Medicines Agency. The drug was originally developed as an analgesic in surgery, but while effective in animal models of nociception, it was repurposed as an antipruritic at lower treatment doses due to an apparently unacceptable incidence of sedative effects in humans. As of 2015, nalfurafine is also in clinical trials for the treatment of cholestatic pruritus in Japan for patients with chronic liver disease, and for the treatment of uremic pruritus in the United States.
== Function == In KYNU reaction, PLP facilitates Cβ-Cγ bond cleavage. The reaction follows the same steps as the transamination reaction but does not hydrolyze the tautomerized Schiff base. The proposed reaction mechanism involves an attack of an enzyme nucleophile on the carbonyl carbon (Cγ) of the tautomerized 3hKyn-PLP Schiff base. This is followed by Cβ-Cγ bond cleavage to generate an acyl-enzyme intermediate together with a tautomerized Ala-PLP adduct. Hydrolysis of the acyl-enzyme then yields 3hAnt.
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 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.