Everything below concerns LC-MS/MS. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-03-09. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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 |
|---|---|---|
| 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 |
The British historian Richard Overy wrote the huge demands of the Four Year Plan "...could not be fully met by a policy of import substitution and industrial rationalisation", thus leading Hitler to decide in November 1937 that to stay ahead in the arms race with the other powers that Germany had to seize Czechoslovakia in the near-future. At the Hossbach conference on 5 November 1937, Hitler announced that seizing Czechoslovakia would increase the supply of food under German control, which in turn would lessen the need to import food, thereby freeing up more foreign exchange to import raw materials necessary for the Four Year Plan's targets. The Hossbach conference was largely taken up with an extended discussion about the necessity of bringing areas adjunct to Germany under German economic control, by force if necessary, as Hitler argued that this was the best way to win the arms race. Hitler stated: "areas producing raw materials can be more usefully sought in Europe, in immediate proximity to the Reich". Overy wrote about Hitler's attitude to the Reich's economic problems that: "He simply saw war instrumentally, as the Japanese had done in Manchuria, as a way to expand the German resource base and to secure it against other powers". At the time, Czechoslovakia had Europe's 7th largest economy, and easily the most modern, developed, and industrialized economy in Eastern Europe.
=== Limitations to bioavailability === A recent study has shown Chlorambucil to be detoxified by human glutathione transferase Pi (GST P1-1), an enzyme that is often found over-expressed in cancer tissues. This is important since Chlorambucil, as an electrophile, is made less reactive by conjugation with glutathione, thereby making the drug less toxic to the cell.
However, several species of bacteria are pathogenic and cause infectious diseases, including cholera, syphilis, anthrax, leprosy, tuberculosis, tetanus and bubonic plague. The most common fatal bacterial diseases are respiratory infections. Antibiotics are used to treat bacterial infections and are also used in farming, making antibiotic resistance a growing problem. Bacteria are important in sewage treatment and the breakdown of oil spills, the production of cheese and yogurt through fermentation, the recovery of gold, palladium, copper and other metals in the mining sector (biomining, bioleaching), as well as in biotechnology, and the manufacture of antibiotics and other chemicals. Once regarded as plants constituting the class Schizomycetes ("fission fungi"), bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells contain circular chromosomes, do not contain a nucleus and rarely harbour membrane-bound organelles. Although the term bacteria traditionally included all prokaryotes, the scientific classification changed after the discovery in the 1990s that prokaryotes consist of two very different groups of organisms that evolved from an ancient common ancestor. These evolutionary domains are called Bacteria and Archaea. Unlike Archaea, bacteria contain ester-linked lipids in the cell membrane, possess elongation factors that are resistant to ADP-ribosylation by diphtheria toxin, use formylmethionine in protein synthesis initiation, and have numerous genetic differences, including a different 16S rRNA.
Sources: en.wikipedia.org
=== Diabetes Mellitus === Increased levels of proinsulin in the circulatory system relative to mature insulin concentrations can indicate impending insulin resistance and the development of type 2 diabetes. Additional problems with proinsulin that can lead to diabetes include mutations in the number of cysteines present, which could affect correct folding. If the mutation causes only a mild change it could simply stress the endoplasmic reticulum’s ability to properly fold the protein. This stress, after a while, would lead to a decrease in the number of β-cells producing mature insulin, and would then lead to diabetes mellitus.
== Structural studies == As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes PDB: 1OPM, PDB: 1PHM, PDB: 1SDW, PDB: 1YI9, PDB: 1YIP, PDB: 1YJK, PDB: 1YJL, and PDB: 3PHM.
=== Defence and intraspecific combat === A few species are able to use chemical defences against predators; some Procellariiformes can eject an unpleasant stomach oil against an aggressor, and some species of pitohuis from New Guinea have a powerful neurotoxin in their skin and feathers. A lack of field observations limit our knowledge, but intraspecific conflicts are known to sometimes result in injury or death. The screamers (Anhimidae), some jacanas (Jacana, Hydrophasianus), the spur-winged goose (Plectropterus), the torrent duck (Merganetta) and nine species of lapwing (Vanellus) use a sharp spur on the wing as a weapon. The steamer ducks (Tachyeres), geese and swans (Anserinae), the solitaire (Pezophaps), sheathbills (Chionis), some guans (Crax) and stone curlews (Burhinus) use a bony knob on the alular metacarpal to punch and hammer opponents. The jacanas Actophilornis and Irediparra have an expanded, blade-like radius. The extinct Xenicibis was unique in having an elongate forelimb and massive hand which likely functioned in combat or defence as a jointed club or flail. Swans, for instance, may strike with the bony spurs and bite when defending eggs or young.
=== Gawker === In May 2016, Ayyadurai filed suit against Gawker Media for $35 million, alleging that their website Gawker published "false and defamatory statements", causing "substantial damage to Dr. Ayyadurai's personal and professional reputation and career". The filing also named writer Sam Biddle, executive editor John Cook, and Gawker founder and CEO Nick Denton. Gawker Media responded that, "These claims to have invented email have been repeatedly debunked by the Smithsonian Institute [sic], Gizmodo, the Washington Post and others." In November 2016, the by-then-bankrupt Gawker Media settled the lawsuit with Ayyadurai for $750,000 as part of a broader settlement with wrestler Hulk Hogan and journalist Ashley Terrill, all of whom were represented by attorney Charles Harder. In a statement, Ayyadurai said that "history will reflect that this settlement is a victory for truth". Biddle denounced the settlement and said he fully stood by his reporting. Denton wrote that "we expected to prevail" in the Ayyadurai and Terrill lawsuits, "but all-out legal war with" billionaire Peter Thiel, who financially backed Harder, was untenable in terms of cost, time and human toll. Katie Hafner, the author of several books on Internet history—including one on the development of ARPANET email—said, "This situation is both bizarre and appalling in that here we are simply trying to get the record straight, and [Ayyadurai has] managed to make money off claims that appear to be misleading."
Sources: en.wikipedia.org
TMA is a low-potency serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of >12,000 nM, an EC50Tooltip half-maximal effective concentration of 1,700 nM, and an EmaxTooltip maximal efficacy of 40%. Conversely, it was inactive at the serotonin 5-HT1A, 5-HT2B and 5-HT2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000 nM). It showed affinity for the mouse and rat trace amine-associated receptor 1 (TAAR1) (Ki = 1,800 nM and 3,200 nM, respectively), whereas it was inactive at the human TAAR1 (EC50 > 10,000 nM). TMA is also a very low-potency serotonin releasing agent (SRA), with an EC50 value of 16,000 nM. In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine (EC50 > 100,000 nM). Despite its apparent SRA activity in vitro, TMA did not increase brain serotonin or dopamine levels in rodents in vivo. TMA is similarly inactive as a monoamine oxidase inhibitor (MAOI), including of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) (IC50Tooltip half-maximal inhibitory concentration > 200,000 nM). The low potency of TMA as a serotonin 5-HT2A receptor agonist is analogous to the case of mescaline, which is a well-known and widely used psychedelic but is likewise a very low-potency agonist of this receptor, showing an affinity (Ki) of 9,400 nM, an EC50 of 10,000 nM, and an Emax of 56% in the same study. For comparison, DOM has shown an affinity (Ki) of 88 nM and an EC50 of 4 to 24 nM.
As with bacterial classification, identification of bacteria is increasingly using molecular methods, and mass spectroscopy. Most bacteria have not been characterised and there are many species that cannot be grown in the laboratory. Diagnostics using DNA-based tools, such as polymerase chain reaction, are increasingly popular due to their specificity and speed, compared to culture-based methods. These methods also allow the detection and identification of "viable but nonculturable" cells that are metabolically active but non-dividing. The main way to characterize and classify these bacteria is to isolate their DNA from environmental samples and mass-sequence them. This approach has identified thousands, if not millions of candidate species. Based on some estimates, more than 43,000 species of bacteria have been described, but attempts to estimate the true number of bacterial diversity have ranged from 107 to 109 total species—and even these diverse estimates may be off by many orders of magnitude.
Promethium (61Pm) is an artificial element, except in trace quantities as a product of spontaneous fission of 238U and 235U and alpha decay of 151Eu, and thus a standard atomic weight cannot be given. Like all artificial elements, it has no stable isotopes. It was first synthesized in 1945. Like technetium, it is preceded and followed by elements with stable isotopes. The known isotopes run from 128Pm to 166Pm, 39 in all; the most stable are 145Pm with a half-life of 17.7 years, 146Pm with a half-life of 5.53 years, and 147Pm (the common isotope) with a half-life of 2.6234 years. 143Pm and 144Pm also have lengthy if poorly-known lives on the order of a year, but all the others have half-lives that are less than six days, with the majority less than a few minutes. There are also 24 known meta states with the most stable being 148mPm at a half-life of 41.29 days. The primary decay mode for isotopes lighter than 146Pm is electron capture resulting in isotopes of neodymium, and the primary decay mode heavier than 146Pm is beta decay giving isotopes of samarium; promethium-146 itself decays both ways.
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 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.