F tier · safety concern
Development was terminated in 2007 after rodent carcinogenicity studies produced tumours across multiple organ systems, and WADA took the rare step of issuing a public health warning stating that clinical approval has not and will not be given for this substance.
gw-501516
GW501516 is a PPARδ agonist that reached phase 2 trials for dyslipidaemia and metabolic indications before GlaxoSmithKline terminated development in 2007 following carcinogenicity findings in rodents. Tumours were reported across multiple organ systems in both mice and rats, and WADA subsequently issued an exceptional public health warning to athletes about the compound.
the explanation
This compound was abandoned by the company that made it after animal studies produced cancers in many different organs. The world anti-doping body took the unusual step of publicly warning athletes about it, stating that it will never be approved for human use.
regulatory status
Not approved by FDA or any regulator; development terminated for carcinogenicity; WADA-prohibited with an exceptional public health warning; not a lawful dietary supplement ingredient
GW501516 was never approved for any indication and its development was terminated by GlaxoSmithKline in 2007 after carcinogenicity findings; WADA has stated publicly that clinical approval has not and will not be given. It was added to the WADA Prohibited List in 2009 as a metabolic modulator, and in 2013 WADA issued a rare public health alert — an action reserved for compounds whose health hazard is judged severe enough to warrant warning users directly rather than merely prohibiting the substance. FDA classifies such compounds in bodybuilding products as unapproved drugs and warns of heart attack, stroke, liver injury and acute liver failure. Numerous adverse analytical findings have been recorded, including four Costa Rican cyclists (2012), Valery Kaykov (2013), Elena Lashmanova (2014) and Jarrell Miller (2019). The SARMs Control Act (S.2742, 2018; S.2895, 2019) was never enacted, and GW501516 is not an androgen receptor ligand and would not have fallen within its definition.
how it works · proposed mechanism
GW501516 is a selective agonist of the nuclear receptor PPARδ, a regulator of fatty acid metabolism in skeletal muscle and liver.
PPARδ agonism
GW501516 selectively activates peroxisome proliferator-activated receptor delta, driving transcription of genes governing fatty acid transport, beta-oxidation and mitochondrial function. This produces a shift toward fat as a fuel substrate in skeletal muscle.
Substrate utilisation shift
Increased fatty acid oxidation with relative sparing of muscle glycogen is the pharmacological basis for the endurance claims attached to the compound. These effects were characterised in rodent models and in short human metabolic studies, not in performance trials.
Proliferative signalling
PPARδ activation also intersects with cell proliferation and survival pathways, which is the mechanistic context for the multi-organ tumour findings that ended development. The breadth of organs affected in rodents indicates the effect is not confined to a single tissue type.
what’s reported
evidence shape
8 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The tumour findings appeared at 3 mg/kg/day across liver, stomach, tongue, skin, bladder, ovaries, womb and testes in both mice and rats, a breadth of organ involvement that is unusual even among compounds withdrawn for carcinogenicity. WADA does not normally comment on the health effects of prohibited substances at all, so its 2013 decision to issue a direct public warning stating that approval will never be given is itself a signal about how the evidence was read.
key published findings
- Rodent (two-year carcinogenicity studies): GW501516 administered at 3 mg/kg/day in both mice and rats produced tumours across multiple organ systems — liver, stomach, tongue, skin, bladder, ovaries, womb and testes.
- Human trial (phase 2): by 2007 GW501516 had completed two phase 2 clinical studies plus additional studies in obesity, diabetes, dyslipidaemia and cardiovascular disease, before development was terminated; no efficacy result from this programme supported approval for any indication.
- Official (WADA, 2013): WADA issued a rare public alert stating that serious toxicities were discovered in pre-clinical studies and that clinical approval has not, and will not, be given for this substance, explicitly warning athletes of the health risks.
- Official (WADA, 2009): GW501516 was added to the WADA Prohibited List as a metabolic modulator; multiple adverse analytical findings followed, including four Costa Rican cyclists in December 2012, cyclist Valery Kaykov in 2013, race walker Elena Lashmanova in 2014 and boxer Jarrell Miller in 2019.
- Review (Mitchell et al., Pulmonary Circulation, 2019): a review assessing PPARβ/δ as a therapeutic target concluded the target is blighted by cancer risk, reflecting how the GW501516 carcinogenicity findings have constrained the entire drug class.
limitations of the evidence
- The full carcinogenicity study reports were not published in the peer-reviewed literature as primary papers, so tumour incidence rates, dose-response relationships and no-observed-effect levels are not available in the public record.
- Rodent carcinogenicity does not automatically translate to human carcinogenicity, though it is the standard preclinical screen on which regulators and sponsors base development decisions, and here it was decisive for the sponsor.
- The human phase 2 programme results were never fully published, so the human metabolic efficacy data that did exist cannot be independently evaluated.
documented safety signals
- Multi-organ carcinogenicity in two rodent species: tumours in liver, stomach, tongue, skin, bladder, ovaries, womb and testes at 3 mg/kg/day, the finding that ended clinical development in 2007.
- WADA issued an exceptional public health warning in 2013 — an action outside its normal remit — stating that serious toxicities were found preclinically and that clinical approval has not and will not be given.
- GlaxoSmithKline, the originator, abandoned the compound entirely rather than pursuing a narrower indication or a modified dosing strategy, indicating the sponsor judged the risk unmanageable.
- PPARδ activation intersects with cell proliferation and survival pathways, providing a mechanistic basis for the tumour findings rather than leaving them as an unexplained anomaly; a 2019 review concluded the whole target class is blighted by cancer risk.
- There is no long-term human safety data of any kind, and because tumour latency is measured in years, absence of reported human cancers in a compound used non-medically since roughly 2009 is not evidence of safety.
- FDA public safety notification on bodybuilding products names heart attack, stroke, psychosis, sleep disturbance, sexual dysfunction, liver injury and acute liver failure among risks from unapproved drugs sold in this category.
- GW501516 is discussed in the NIH LiverTox SARMs chapter among related performance compounds, a class assigned a likelihood score of B for clinically apparent liver injury.
- Sold entirely through unregulated channels with no verified identity, purity or content, and no medical supervision under which an emerging malignancy would be screened for.
identity
| full name | GW501516 (cardarine, endurobol, GW1516) |
| category | Anabolic & Receptor |
| modality | small molecule |
| formula | C21H18F3NO3S2 |
| molar mass | 453.5 g/mol |
| cas | 317318-70-0 |
laboratory handling
| storage | Reference material: store as a solid, desiccated and protected from light, at -20 °C for long-term stability; stock solutions typically stored at -80 °C. Handle as a known rodent carcinogen using appropriate laboratory containment. |
| solubility | Lipophilic small molecule; soluble in DMSO and ethanol, poorly soluble in water. Lot-specific solubility should be taken from the certificate of analysis. |
| co-studied with | Evidence caveat only: no combination involving GW501516 has any supporting evidence base, and the multi-organ rodent carcinogenicity finding is not offset or mitigated by any co-administered compound in any published study. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedWorld Anti-Doping Agency · 2013 · official
CBC News (reporting the WADA GW501516 health alert) · 2013 · official
U.S. Food and Drug Administration · 2025 · official
Pulmonary Circulation · 2019 · reviews
Newsholme, Dunsford et al. (carcinogenicity study report; full primary publication not available in the open peer-reviewed record) · 2007 · preclinical
Wikipedia (secondary compilation of primary regulatory, sponsor and anti-doping sources) · 2025 · reviews
others in Anabolic & Receptor