This is a working overview of PPARδ agonist, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-11-12. Anything still debated is marked as such rather than presented as settled.
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.
Handling and quality assessment of cardarine reference material follow general laboratory practices for poorly characterized compounds. It typically appears as a white to off-white powder and is sparingly soluble in water but soluble in organic solvents such as dimethyl sulfoxide and ethanol. Storage recommendations usually specify a cool, dry, dark place, with long-term storage at low temperature and desiccation. Purity may be checked by high-performance liquid chromatography with ultraviolet detection, while identity is confirmed by mass spectrometry and nuclear magnetic resonance. No pharmacopeial monograph exists, so reported purity and stability depend on the supplier’s methods.
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 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.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white powder | Visual description for typical solid reference material. |
| Solubility | Poorly soluble in water; soluble in DMSO | Solubility depends on solvent, purity, and form. |
| Storage | Cool, dry, protected from light | Long-term storage often uses low temperature and desiccant. |
| Common analytical method | LC-MS/MS | Used for detection and quantification in biological matrices. |
| Common synonyms | GW-501516; GW501516; endurobol | Naming varies among literature, vendors, and databases. |
==== July 2018 Clostridium perfringens ==== In late July 2018, Ohio public health officials launched an investigation after receiving 350 complaints from customers after they had eaten at a Powell, Ohio, location. By mid-August, the U.S. Centers for Disease Control and Prevention identified the bacteria that cause the outbreak which had affected over 700 people as Clostridium perfringens. This food borne outbreak has been called the worst incident to date that can be traced to a single restaurant location.
=== Phase 2 === AB-2004 – microbiome modulator Acamprosate (AOP-2020; Campral; SF-679/SF-775; SF-999) – unknown / GABAA receptor positive allosteric modulator and ionotropic glutamate NMDA receptor antagonist Alogabat (RG-7816, RG7816, RO-7017773; GABA-A-α5 PAM) – GABAA α5 subunit-containing receptor positive allosteric modulator Arbaclofen ((R)-baclofen; STX-209) – GABAB receptor agonist Cannabidiol (CBD; Epidiolex) – cannabinoid receptor modulator, other actions Cannabidiol transdermal patch/gel (Zygel; ZYN-002) – cannabinoid receptor modulator, other actions Cannabidivarin (CBDV; GWP-42006) – non-intoxicating cannabinoid receptor modulator, other actions CP-101 – bacteria relacement and gastrointestinal microbiome modulator JNJ-42165279 (JNJ-5279) – fatty acid amide hydrolase (FAAH) inhibitor Non-racemic MDMA (ALA-002; 70–80% (R)-MDMA, 20–30% (S)-MDMA) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen Oxytocin (intranasal potentiated oxytocin; TI-001, TI-114, TNX-1900, TNX-2900) – oxytocin receptor agonist Pitolisant (Wakix; tiprolisant) – histamine H3 receptor inverse agonist Racemetirosine (DL-α-methyltyrosine; L1-79) – tyrosine hydroxylase inhibitor Suramin (IV suramin; PAX-101/PAX-102) – DNA synthesis inhibitor and anti-purinergic agent Zolmitriptan modified-release (ML-004, ML004) – serotonin 5-HT1B and 5-HT1D receptor agonist
=== 5-Hydroxymethylcytosine === Bisulfite sequencing is used widely across mammalian genomes, however complications have arisen with the discovery of a new mammalian DNA modification 5-hydroxymethylcytosine. 5-Hydroxymethylcytosine converts to cytosine-5-methylsulfonate upon bisulfite treatment, which then reads as a C when sequenced. Therefore, bisulfite sequencing cannot discriminate between 5-methylcytosine and 5-hydroxymethylcytosine. This means that the output from bisulfite sequencing can no longer be defined as solely DNA methylation, as it is the composite of 5-methylcytosine and 5-hydroxymethylcytosine.
Creatine phosphate (CP), like ATP, is stored in muscle cells. When it is broken down, a considerable amount of energy is released. The energy released is coupled to the energy requirement necessary for the resynthesis of ATP. The total muscular stores of both ATP and CP are small. Thus, the amount of energy obtainable through this system is limited. The phosphagen stored in the working muscles is typically exhausted in seconds of vigorous activity. However, the usefulness of the ATP-CP system lies in the rapid availability of energy rather than quantity. This is important with respect to the kinds of physical activities that humans are capable of performing. The phosphagen system (ATP-PCr) occurs in the cytosol (a gel-like substance) of the sarcoplasm of skeletal muscle, and in the myocyte's cytosolic compartment of the cytoplasm of cardiac and smooth muscle. During muscle contraction:
Sources: en.wikipedia.org
== History == The chemical synthesis of large peptides is still limited by problems of low solvation during solid phase peptide synthesis (SPPS) or limited solubility of fully protected peptide fragments: even chemoselective ligation methods are hampered by self-association of unprotected peptide blocks. The elucidation of the relationship between preferred conformation of a growing peptide chain and its physicochemical properties reveals that β-sheet (beta-sheet) formation is often paralleled by significant decrease in solvation and solubility. Besides attempts to increase the solvation of peptides by external factors, few attempts, i.e. N-substituted Hmb amino acid derivatives and pseudoprolines (see figure on the top right) have been reported to modify the intrinsic properties of peptides responsible for aggregation and secondary structure formation. Pseudoprolines consist of serine- (Oxa) or threonine-derived oxazolidines [Oxa(5-Me)] and Cysteine-derived thiazolidines (THz) with Proline-like ring structure (see top right). Mutter and coworkers have defined oxa- and thiaproline derivatives of serine, threonine, and cysteine with Ser(ψPro). Thr(ψPro), and Cys(ψPro), respectively, where the abbreviation ψPro indicates the relationship to proline (with heteroatomic ring substitution in position 4). Pseudoprolines with substitution in position 2 of the proline ring are named Ser/Thr/Cys-(ψR1, R2 Pro).
Cartels have engaged in kidnapping, ransom, murder, robbery, and extortion of migrants traveling from Central America through Mexico on their way to the United States and Canada. Cartels have also forced migrants to join their organization and work for them, a situation that has been described as slavery. Mass graves have been also discovered in Mexico containing bodies of migrants. In 2011, 177 bodies were found in a mass grave in San Fernando, Tamaulipas, the same area where the bodies of 72 migrants were found in 2010, where most victims "died of blunt force trauma to the head." Cartels have also infiltrated the Mexican government's immigration agencies and attacked and threatened immigration officers. The National Human Rights Commission of Mexico (Comisión Nacional de los Derechos Humanos, CNDH) said that 11,000 migrants had been kidnapped in 6 months in 2010 by drug cartels.
== Identification == Fossil dinosaur eggshell fragments can be recognized based on three important traits. Their thickness should be roughly uniform, they are usually slightly curved, and their surface is covered in tiny pores. Less frequently, the concave underside of the eggshell fragment will preserve bumps known as mammillae. Sometimes the embryo had absorbed so much of the calcium that the mammillae need a magnifying glass or microscope to be seen. However, there are many kinds of naturally occurring objects which can resemble fossil eggs. These can fool even professional paleontologists.
=== Pharmacodynamics (PD) === Pharmacodynamic models focus on elucidating the intricate relationship between drug concentration and its effects on the body. This includes both the desired therapeutic effects and potential side effects. By delineating the time course of drug effects, these models contribute to the prediction of efficacy and adverse events, aiding in the identification of optimal dosing strategies.
Data from NHANES surveys (1976–1980 and 2003–2006) show that the prevalence of obesity has increased: for children aged 2–5 years, prevalence increased from 5.0% to 12.4%; for those aged 6–11 years, prevalence increased from 6.5% to 19.6%; and for those aged 12–19 years, prevalence increased from 5.0% to 17.6%. In 2000, approximately 39% of children (ages 6–11) and 17% of adolescents (ages 12–19) were overweight and an additional 15% of children and adolescents were at risk of becoming overweight, based on their BMI. Analyses of the trends in high BMI for age showed no statistically significant trend over the four time periods (1999–2000, 2001–2002, 2003–2004, and 2005–2006) for either boys or girls. Overall, in 2003–2006, 11.3% of children and adolescents aged 2 through 19 years were at or above the 97th percentile of the 2000 BMI-for-age growth charts, 16.3% were at or above the 95th percentile, and 31.9% were at or above the 85th percentile. Trend analyses indicate no significant trend between 1999 and 2000 and 2007–2008 except at the highest BMI cut point (BMI for age 97th percentile) among all 6- through 19-year-old boys. In 2007–2008, 9.5% of infants and toddlers were at or above the 95th percentile of the weight-for-recumbent-length growth charts. Among children and adolescents aged 2 through 19 years, 11.9% were at or above the 97th percentile of the BMI-for-age growth charts; 16.9% were at or above the 95th percentile; and 31.7% were at or above the 85th percentile of BMI for age.
Sources: en.wikipedia.org
Hyperpolarization A change in a cell’s membrane potential that makes it more negative, decreasing the likelihood of firing an action potential. Hypoglossal nerve (Cranial Nerve XII) A cranial nerve responsible for controlling the muscles of the tongue. Damage can cause slurred speech and difficulty swallowing. Hypothalamus A region of the brain below the thalamus that regulates homeostatic functions such as hunger, thirst, body temperature, and circadian rhythms. It controls the pituitary gland and links the nervous and endocrine systems.
Foster (1895–1970), Manhattan Project chemist and the first female chemist to work for the United States Geological Survey Antoine François, comte de Fourcroy (1775–1809), co-discovered the element Iridium and developed modern chemical notation Joanna Fowler (born 1942), American neural chemist who studied effects on the human brain and radiotracers in brain chemistry Michelle Francl (PhD 1983), American computational chemist known for the 6-31G* basis set for Na to Ar and electrostatic potential charges Edward Frankland (1825–1899), English chemist, one of the originators of organometallic chemistry who introduced the concept of valence Rosalind Franklin (1920–1958), British chemist and crystallographer whose work was central to understanding the molecular structure of DNA Katherine Franz (born 1972), American chemist noted for work in metal ion coordination in biological systems Herman Frasch (1851–1914), German mining engineer and inventor, pioneered the Frasch process Bertram Fraser-Reid (1934–2020), Jamaican synthetic organic chemist who developed the armed-disarmed principle in glycosylation chemistry Helen Murray Free (1923–2021), American chemist who developed self-testing systems for diabetes Carl Remigius Fresenius (1818–1897), German chemist known for work in analytical chemistry Ida Freund (1863–1914), British chemist known for texts on chemistry teaching, andy first woman university chemistry lecturer in the UK Charles Friedel (1832–1899), French chemist, developer of Friedel–Crafts reaction Alexander Naumovich Frumkin (1895–1976), electrochemist and chemist who develped applied electrochemical processes related to chemical sources of electrical power Kenichi Fukui (1918–1998), 1981 Nobel Prize in Chemistry for investigating mechanisms of chemical reactions Elizabeth Fulhame (18th–19th centuries), British chemist, pioneer in the study of catalysis and discoverer of photoreduction Vera Furness (1921–2002), English chemist and industrial manager who worked on the production of the acrylic Courtelle
and above a critical temperature, the self-assembly process will become progressively less likely to occur and spontaneous self-assembly will not happen. The self-assembly is governed by the normal processes of nucleation and growth. Small assemblies are formed because of their increased lifetime as the attractive interactions between the components lower the Gibbs free energy. As the assembly grows, the Gibbs free energy continues to decrease until the assembly becomes stable enough to last for a long period of time. The necessity of the self-assembly to be an equilibrium process is defined by the organization of the structure which requires non-ideal arrangements to be formed before the lowest energy configuration is found. Kinetics The ultimate driving force in self-assembly is energy minimization and the corresponding evolution towards equilibrium, but kinetic effects can also play a very strong role. These kinetic effects, such as trapping in metastable states, slow coarsening kinetics, and pathway-dependent assembly, are often viewed as complications to be overcome in, for example, the formation of block copolymers. Amphiphile self-assembly is an essential bottom-up approach of fabricating advanced functional materials. Self-assembled materials with desired structures are often obtained through thermodynamic control. Here, we demonstrate that the selection of kinetic pathways can lead to drastically different self-assembled structures, underlining the significance of kinetic control in self-assembly.
Additionally, one trial aimed to assess its role in preventing actinic keratosis in organ transplant recipients. Further trials were pursued for the first two conditions, while results for the latter three were not published. Following the initial trials, research efforts centered on erythropoietic protoporphyria, and due to the epidemiology of the condition. Clinuvel secured orphan drug for afamelanotide in both the US and the EU by 2010. The first approval of afamelanotide came in May 2010 from the Italian Medicines Agency (AIFA, or Agenzia Italiana del Farmaco), followed by the European Medicines Agency (EMA) in January 2015. Both approvals were for the treatment of erythropoietic protoporphyria. The US Food and Drug Administration (FDA) granted approval in October 2019 for the use of afamelanotide as a medication to alleviate pain caused by sun exposure in individuals with erythropoietic protoporphyria. This decision was largely based on three trials involving 244 adults aged 18–74 across 22 sites in the US and Europe, which had a focus on pain-free hours in sunlight, outdoor hours under varying light conditions, and side effects. The FDA designated it as a first-in-class medication, meaning it had a novel mechanism different from previously approved medications. Between 2022 and 2023, trials were outlined to study the effects of afamelanotide on xeroderma pigmentosum and variegate porphyria, along with two additional trials exploring its impact on vitiligo. According to the register, as of April 2025, most of these trials are currently in the recruitment phase.
Sources: en.wikipedia.org
Cardarine targets PPARδ, a nuclear receptor involved in lipid and energy metabolism. It does not bind the androgen receptor in the way SARMs do.
Most methods use liquid chromatography with tandem mass spectrometry. Urine is common in anti-doping testing, and blood or plasma may be used in research.
Typical guidance is cool, dry, dark storage, often at low temperature and with desiccant. Stability data are limited, so storage conditions should be verified for each batch or supplier.
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.