SR9009 (Stenabolic) and GW501516 (Cardarine) are two of the most frequently compared metabolic research compounds. Both are studied in the context of endurance, lipid metabolism, and mitochondrial function — yet they work through entirely different receptor systems and have fundamentally different safety profiles in the published literature.
Neither compound is a true SARM (neither binds androgen receptors), but both are regularly grouped with SARMs in research communities because of overlapping vendor availability and study contexts. This guide provides a direct mechanistic and evidence-based comparison. For foundational context on this compound space, see our Complete Guide to SARMs.
Quick Comparison: SR9009 vs GW501516
| Property | SR9009 (Stenabolic) | GW501516 (Cardarine) |
|---|---|---|
| Receptor target | Rev-Erbα / Rev-Erbβ | PPARδ |
| Compound class | Rev-Erb agonist | PPARδ agonist |
| Acts on androgen receptors? | No | No |
| Primary mechanism | Circadian clock regulation, mitochondrial biogenesis | Fatty acid oxidation gene upregulation |
| HPG axis suppression | No | No |
| Carcinogenicity findings | Not reported in same way | Yes — GSK halted development |
| Human clinical data | None published | None published (program terminated) |
| Oral bioavailability (rodent) | Low — significant variability reported | Good |
SR9009 (Stenabolic): Overview
SR9009 is a synthetic agonist of Rev-Erb nuclear receptors — specifically Rev-Erbα and Rev-Erbβ, which are core components of the circadian clock machinery. Rev-Erb proteins act as transcriptional repressors: when activated, they suppress the expression of genes they regulate. Because Rev-Erb proteins are central to circadian rhythm regulation and directly control metabolic gene networks, SR9009 has attracted research interest as a tool for studying circadian biology and its intersection with lipid metabolism, glucose homeostasis, and mitochondrial function.
Key preclinical findings: Studies in mice have reported that SR9009 administration increases running endurance, reduces fat mass, and improves metabolic parameters including cholesterol and triglyceride levels. A landmark 2013 paper by Woldt et al. in Nature Medicine demonstrated that Rev-Erb agonism with SR9009 increased mitochondrial content and oxidative capacity in skeletal muscle in mice, and improved exercise capacity in both lean and obese models.
Critical caveat — oral bioavailability: SR9009 has a well-documented oral bioavailability challenge in rodent models. Multiple pharmacokinetic studies have reported low and variable oral bioavailability, which complicates interpretation of oral dosing studies and means that the route of administration is a significant variable in SR9009 research protocols. Researchers designing SR9009 studies should carefully consider delivery method and reference the relevant PK literature.
Best suited for research into: Circadian clock biology, mitochondrial biogenesis, Rev-Erb receptor pharmacology, metabolic syndrome models where circadian pathway involvement is the question.
→ View SR9009 (Stenabolic) research compound
GW501516 (Cardarine): Overview
GW501516 is a PPARδ (Peroxisome Proliferator-Activated Receptor delta) agonist, originally developed in collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It activates PPARδ, a transcription factor that regulates fatty acid oxidation genes in skeletal muscle, adipose tissue, and the liver. When PPARδ is activated, cells upregulate their capacity to oxidize fatty acids for fuel — shifting energy metabolism away from glucose and glycogen.
Key preclinical findings: GW501516 has a robust preclinical literature. Studies demonstrated significant improvements in lipid profiles (increased HDL, decreased LDL and triglycerides), reduced adiposity in diet-induced obese rodent models, and enhanced endurance performance. The Narkar et al. (2008) Cell paper documenting exercise mimetic effects of GW501516 is among the most cited findings in this space.
Critical caveat — carcinogenicity: GlaxoSmithKline terminated GW501516’s clinical development program following internal preclinical carcinogenicity studies that demonstrated rapid multi-tissue tumor growth in rodents. The mechanism is proposed to be proliferative (PPARδ-mediated acceleration of pre-existing or latent neoplastic cell growth) rather than genotoxic. This finding is documented in the scientific record and is essential context for any research protocol involving GW501516. Researchers should review the carcinogenicity literature and account for these findings in experimental design — particularly in studies with any proliferative endpoints.
Best suited for research into: PPARδ biology, fatty acid oxidation, lipid metabolism, metabolic syndrome — with full awareness of the carcinogenicity literature.
→ View GW501516 (Cardarine) research compound
Mechanism Deep Dive: Rev-Erb vs PPARδ
The mechanistic differences between SR9009 and GW501516 are fundamental — not superficial. Understanding this distinction is essential for selecting the appropriate compound for a given research question.
Rev-Erb (SR9009’s target) is a nuclear receptor that functions primarily as a transcriptional repressor. It is part of the core circadian clock feedback loop — Rev-Erb proteins suppress the expression of Bmal1, a key circadian clock gene, creating a daily oscillation. Beyond circadian regulation, Rev-Erb proteins directly repress genes involved in lipogenesis, gluconeogenesis, bile acid synthesis, and inflammatory signaling. When SR9009 activates Rev-Erb, it amplifies this repression — suppressing lipid storage genes, increasing mitochondrial biogenesis markers, and altering circadian-dependent metabolic oscillations.
PPARδ (GW501516’s target) is a transcriptional activator. When GW501516 binds PPARδ, the receptor-ligand complex activates (rather than represses) genes encoding fatty acid oxidation enzymes, mitochondrial electron transport chain components, and muscle fiber type determination factors. The net effect is increased cellular capacity to burn fat and an upregulation of oxidative metabolism in muscle.
Both pathways converge on mitochondrial function and fat oxidation as downstream outcomes — which is why the compounds are often compared — but they do so through opposite transcriptional mechanisms (repression vs activation) at different upstream targets (Rev-Erb vs PPARδ). For researchers studying how these pathways interact or compete, the two compounds are complementary tools rather than interchangeable ones.
Safety Profiles: A Critical Distinction
This is the most practically significant difference between the two compounds for research protocol design.
GW501516 has documented carcinogenicity findings from GSK’s own preclinical safety studies — rapid tumor growth across multiple tissue types in rodent models. Any research protocol using GW501516 should explicitly account for this, including in endpoint selection, animal model choice, and duration of administration.
SR9009 does not have the same documented carcinogenicity profile in the published literature. Rev-Erb agonism does not have the same proliferative mechanism proposed for PPARδ activation. However, the absence of published carcinogenicity findings for SR9009 reflects in part the less mature development stage of this compound — comprehensive safety studies comparable to GSK’s GW501516 program have not been published for SR9009.
Neither compound has published human safety data from clinical trials — GW501516’s program was terminated before clinical exposure, and SR9009 has not entered clinical trials.
Oral Bioavailability: A Practical Research Variable
SR9009’s low and variable oral bioavailability in rodent models is a meaningful limitation for oral dosing study designs. Researchers who have used SR9009 via oral gavage in mice have reported inconsistent plasma exposure. Some research groups have used alternative administration routes (subcutaneous, intraperitoneal) to achieve more consistent systemic exposure.
GW501516 demonstrates substantially better oral bioavailability in rodent models, making oral administration protocols more straightforward to design and interpret.
For researchers where route of administration flexibility is a concern, this is a practical advantage of GW501516 over SR9009 in rodent studies.
Which Compound for Which Research Question?
Choose SR9009 if: Your research question involves circadian biology, Rev-Erb receptor pharmacology, or the specific role of the circadian clock in metabolic regulation. Also appropriate if you want to study mitochondrial biogenesis through a Rev-Erb-dependent pathway specifically. Be aware of the oral bioavailability limitations and plan your delivery method accordingly.
Choose GW501516 if: Your research question involves PPARδ biology, fatty acid oxidation gene regulation, or lipid metabolism via the PPAR pathway. Also appropriate for studies examining the carcinogenicity mechanism of PPARδ activation itself. Factor the safety literature into your protocol design.
If your research goal is simply to increase fat oxidation or endurance capacity in an animal model as a secondary effect (rather than studying the upstream pathway specifically), both compounds can achieve directionally similar outcomes — but via different mechanisms that will produce different results in pathway-level analyses.
Sourcing Both Compounds
Chemyo Sarms supplies both SR9009 and GW501516 as research-grade compounds with independent third-party COA documentation confirming identity, purity, and concentration for each batch.
Frequently Asked Questions
Is SR9009 or GW501516 better for endurance research?
Both have shown endurance-enhancing effects in preclinical mouse models, but through different mechanisms and with different practical limitations. GW501516 has more consistent oral bioavailability in rodent models, making it easier to work with in standard oral dosing protocols. SR9009 may show variable results depending on administration route. The “better” choice depends on whether your research question is pathway-specific (Rev-Erb vs PPARδ) or endpoint-focused (endurance capacity as a secondary measure).
Do SR9009 or GW501516 affect testosterone levels?
Neither compound acts on androgen receptors or the HPG axis. Neither SR9009 nor GW501516 suppresses LH, FSH, or endogenous testosterone production. This is a key distinction from SARMs like LGD-4033, which produce HPG suppression as a direct consequence of AR agonism.
Why did GSK abandon GW501516?
GlaxoSmithKline terminated GW501516’s development program after internal preclinical carcinogenicity studies showed rapid multi-tissue tumor growth in rodents. The proposed mechanism involves PPARδ-mediated proliferative activity — potentially accelerating the growth of pre-existing neoplastic cells — rather than direct DNA damage. This finding is documented in published scientific reviews and GSK’s public communications.
What does Rev-Erb do?
Rev-Erbα and Rev-Erbβ are nuclear receptors that function as transcriptional repressors and are core components of the circadian clock. They suppress the expression of Bmal1 (a circadian clock activator) and directly regulate genes involved in lipid metabolism, gluconeogenesis, inflammation, and mitochondrial biogenesis. SR9009 acts as a pharmacological agonist of these receptors, amplifying their repressive activity.
Can SR9009 and GW501516 be used in the same study?
Combination or comparative protocols are at the researcher’s discretion. Because the compounds act on different receptors through different mechanisms, comparative studies examining downstream metabolic effects of Rev-Erb vs PPARδ activation would be a legitimate research design. Researchers should account for GW501516’s carcinogenicity profile in any combined protocol design.
Both compounds are sold by Chemyo Sarms strictly as research compounds for laboratory use. Not intended for human consumption. Researchers should review the full published literature, including safety data, before designing protocols. For educational reference only.