This is a working overview of Carcinogenicity, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2025-11-10 and is reviewed periodically as new material appears.
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.
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.
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.
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.
| 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 FDA also expanded the intended use for the PD-L1 IHC 22C3 pharmDx kit to include use as a companion diagnostic device for selecting patients with head and neck squamous cell carcinoma for treatment with pembrolizumab as a single agent. In July 2019, the US FDA approved pembrolizumab for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥ 10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. The FDA also approved a new use for the PD-L1 IHC 22C3 pharmDx kit as a companion diagnostic device for selecting patients for the above indication. In June 2020, the US FDA approved pembrolizumab as monotherapy for the treatment of adults and children with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. In March 2021, the accelerated approval indication in the US for the treatment of people with metastatic small-cell lung cancer (SCLC) was removed. In January 2024, the FDA approved pembrolizumab, in combination with chemoradiotherapy, for people with FIGO 2014 Stage III-IVA cervical cancer.
==== Academic licencing, licence steering and AI commercialisation ==== The use of academic research for Large Language Models (LLMs) has sparked debate within the Open Access movement. Academics accuse publishers of steering authors towards restrictive licences to retain exclusive commercial rights for AI training deals. In 2024, publishers like Taylor & Francis announced lucrative AI training partnerships, often without consulting authors. This dynamic complicates copyright litigation, as seen in the US when Elsevier sued Meta over Llama AI models, acting as the class representative due to exclusive commercial rights granted by authors.
Many of these conditions are far more common and more likely to be the source of necrotic wounds, even in areas where brown recluse spiders actually occur. The most important of these is methicillin-resistant Staphylococcus aureus (MRSA), a bacterium whose necrotic lesions are very similar to those induced by recluse bites, and which can be lethal if left untreated. Misdiagnosis of MRSA as spider bites is extremely common (nearly 30% of patients with MRSA reported that they initially suspected a spider bite), and can have fatal consequences. Reported cases of brown recluse bites occur primarily in Arkansas, Colorado, Kansas, Missouri, Nebraska, Oklahoma, and Texas. There have been many reports of brown recluse bites in California – though a few related species of spiders may be found there, none of the related spiders in California is known to bite humans. To date, the reports of bites from areas outside of the spider's native range have been either unverified or, if verified, the spiders have been moved to those locations by travelers or commerce.
=== Class I Amidotransferase Domain === The amidotransferase domain is responsible for removal of the amide nitrogen from the glutamine substrate. The class I amidotransferase domain is made of the N terminal 206 residues of the enzyme, and consists of 12 beta strands and 5 alpha helices; the core of this domain is an open 7-stranded mixed beta sheet. Its catalytic triad includes Cys86, His181 and Glu183. His181 is a base and Glu183 is a Hydrogen bond acceptor from the Histidine imidazole ring. Cys86 is the catalytic residue and is conserved. It falls into a nucleophile elbow, where it is at the end of a beta strand and the beginning of an alpha helix, and has little flexibility in its phi and psi angles; thus, Gly84 and Gly88 are conserved and allow for the tight packing of amino acids surrounding the catalytic residue.
Sources: en.wikipedia.org
By conceptualizing tissue-biofluid as information channels, significant biofluid proxies can be identified and then used for the guided development of clinical diagnostics. Candidate biomarkers are then predicted based on information transfer criteria across the tissue-biofluid channels. Significant biofluid-tissue relationships can be used to prioritize clinical validation of biomarkers.
== External links == Pancreatic+Elastase at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Overview of all the structural information available in the PDB for UniProt: P00772 (Pancreatic elastase) at the PDBe-KB. This article incorporates text from the United States National Library of Medicine, which is in the public domain.
== Chemistry == Icodextrin is a starch-derived, branched, water-soluble glucose polymer linked by α-(1→4) and less than 10% α-(1→6) glycosidic bonds, making it a type of dextrin. Its weight-average molecular weight is between 13,000 and 19,000 daltons and its number-average molecular weight between 5,000 and 6,500 daltons. The substance is a white to off-white solid, and the solution is clear and colourless to pale yellow.
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.