For research and educational purposes only · Not medical advice · Consult a qualified physician before any human use
SLU-PP-332 is a synthetic small molecule that activates all three estrogen-related receptor subtypes (ERRalpha, ERRbeta, ERRgamma), triggering a gene expression program that closely resembles the response to acute aerobic exercise. In multiple mouse studies it has increased endurance, reduced fat mass, improved insulin sensitivity, and shown protection against heart failure and age-related kidney dysfunction. No human trials have been conducted.
SLU-PP-332 is not a peptide. It is a synthetic small molecule derived from the structure of GSK4716, a known ERRgamma/beta agonist, and optimized by researchers at Saint Louis University and Washington University to achieve ERRalpha activity. It is included in The Peptide Signal database because it is widely co-marketed with peptide research compounds, appears in biohacker communities alongside performance peptides, and targets a pathway (mitochondrial biogenesis via PGC-1alpha) that is relevant to the same audience researching MOTS-c, SS-31, and other mitochondrial-targeting compounds. The label "non-peptide small molecule" is accurate and should be understood before interpreting any evidence in this profile.
The entire evidence base for SLU-PP-332 as of March 2026 is preclinical. All published studies have used mouse or rat models with intraperitoneal injection, typically at 25 to 50 mg/kg twice daily, a dose that does not translate directly to humans. No Phase 1 safety trial, no pharmacokinetic study in humans, and no toxicology study in humans exist. The biohacker community has developed oral dosing protocols in the range of 250 mcg to 1.5 mg daily, but these are entirely unsupported by any clinical data and represent independent extrapolation from animal literature.
WADA added SLU-PP-332 to the Prohibited List under Category S4 (Hormone and Metabolic Modulators) based on its demonstrated performance-enhancing effects in animal models, specifically treadmill endurance increases exceeding 70 percent in mice. Any athlete subject to WADA testing should treat this compound as a doping violation risk.
Estrogen-related receptors (ERRs) are orphan nuclear receptors, meaning they have structural similarity to estrogen receptors but do not bind estrogen. Three isoforms exist: ERRalpha, ERRbeta, and ERRgamma. They function as ligand-activated transcription factors that regulate energy metabolism, mitochondrial biogenesis, and oxidative phosphorylation, particularly in tissues with high energy demand: skeletal muscle, heart, liver, and kidney. ERRalpha specifically acts as a master regulator of the exercise response in muscle, coordinating the same gene networks activated by endurance training.
The pharmaceutical challenge with ERRalpha has been its structural intractability as a drug target. Unlike ERRbeta and ERRgamma, ERRalpha lacks a well-defined ligand-binding pocket for small molecules. Designing potent ERRalpha agonists with in vivo activity required approximately a decade of structure-based medicinal chemistry by the Burris laboratory. The breakthrough was exploiting Phe328, an amino acid unique to ERRalpha's ligand-binding domain, by incorporating a naphthalene substituent into the scaffold of GSK4716.
SLU-PP-332 was first reported publicly in the 2023 ACS Chemical Biology paper by Billon, Sitaula, Banerjee, and colleagues under the direction of Thomas P. Burris at Washington University School of Medicine. The compound name encodes its academic origin: "SLU" for Saint Louis University (where early development occurred), "PP" for pharmacology program, "332" as a series identifier. Subsequent work from the Burris group, collaborators at Baylor College of Medicine, the Salk Institute, the University of Florida, and Washington University has expanded its characterization across metabolic syndrome, heart failure, kidney aging, and muscle atrophy models through 2024 and 2025.
SLU-PP-332 activates all three ERR isoforms with EC50 values of 98 nM (ERRalpha), 230 nM (ERRbeta), and 430 nM (ERRgamma), demonstrating approximately 4-fold selectivity for ERRalpha over ERRgamma. Once bound, ERRs function as transcription factors that drive expression of genes controlling mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation. The key downstream targets include PGC-1alpha (the master regulator of mitochondrial biogenesis), GLUT4 (the insulin-responsive glucose transporter), and DDIT4 (a stress-response gene upregulated by acute exercise).
The functional result in skeletal muscle is a shift in fiber type composition toward oxidative type IIa fibers, increased mitochondrial density, enhanced cellular respiration, and a switch in substrate preference from carbohydrates toward fatty acid oxidation. This mirrors the metabolic adaptations that occur in muscle with chronic endurance training, without the mechanical stress of exercise itself.
In cardiac tissue, the mechanism operates somewhat differently, with ERRgamma identified as the primary mediator of cardioprotection rather than ERRalpha. ERR agonism in the heart restores fatty acid metabolism and oxidative phosphorylation gene expression in failing hearts, which have characteristically shifted toward glycolytic metabolism. Additionally, ERR agonists suppress cell cycle and developmental pathways in cardiomyocytes partly through downregulation of E2F1, which may limit pathological hypertrophic signaling.
In kidney tissue, the mechanism involves reversal of age-related mitochondrial dysfunction through the cGAS-STING and STAT3 signaling pathways, reducing inflammatory cytokines and restoring mitochondrial complex expression. The compound cannot cross the blood-brain barrier in its current form, limiting CNS application, though follow-on compounds at Pelagos Pharmaceuticals (a startup co-founded by the original researchers) have been designed with CNS penetration in mind.
In the primary mouse endurance study, SLU-PP-332-treated mice ran approximately 70 percent longer in time and approximately 45 percent further in distance on exhaustion treadmill testing compared to vehicle controls. Quadriceps histology showed a significant increase in succinate dehydrogenase (SDH)-positive type IIa oxidative fibers, confirming a shift toward an endurance muscle fiber phenotype.
Gene expression analysis confirmed that SLU-PP-332 induced an ERRalpha-specific acute exercise gene program: upregulation of PGC-1alpha, cytochrome C, GLUT4, DDIT4, and multiple oxidative phosphorylation complex genes. The exercise gene program was confirmed to be ERRalpha-dependent through ERRalpha-null mouse experiments, where the endurance benefit was absent despite continued ERRbeta/gamma activation.
All evidence is murine and used intraperitoneal dosing. No human performance data exists. The community-reported oral dosing range of 250 mcg to 1.5 mg daily has no pharmacokinetic or efficacy validation.
Mouse endurance data is robust and mechanistically coherent. The ERRalpha-dependency confirmation is strong pharmacological evidence. Translation to humans is entirely speculative and no oral bioavailability data exists.
In diet-induced obese mice, 28 days of SLU-PP-332 at 50 mg/kg twice daily produced approximately 12 percent reduction in body weight with approximately 25 percent increase in fatty acid oxidation and no change in food intake, indicating the effect is driven by increased energy expenditure rather than appetite suppression. Fat mass accumulation was significantly reduced, and adipocyte size decreased on histology.
In ob/ob mice (a severe obesity model), the 12-day protocol improved insulin sensitivity as assessed by glucose and pyruvate tolerance tests, with significant reduction in the area under the curve for both tests versus vehicle. Blood total cholesterol and triglycerides were reduced in DIO mice.
Critically, in lean chow-fed mice at the same dose, no significant body weight change was observed after 28 days, suggesting the metabolic effect requires a background of obesity or metabolic dysfunction to manifest. This important null finding is not prominent in community discussions of the compound.
The animal metabolic data is impressive and internally consistent across multiple model systems, but the null finding in lean mice is underreported and underscores how far this compound is from a human obesity application. The ob/ob protocol was shortened due to reduced animal tolerance, which itself is a safety signal.
In a surgically-induced pressure overload heart failure model, both SLU-PP-332 and a related compound (SLU-PP-915) significantly improved ejection fraction, reduced cardiac fibrosis, and increased survival compared to vehicle-treated heart failure animals. Critically, cardioprotection was achieved without affecting cardiac hypertrophy, suggesting ERR agonism improves metabolic function without contributing to pathological remodeling.
Multi-omics analysis showed broad transcriptional activation of fatty acid metabolism and mitochondrial function genes. Metabolomics confirmed normalization of fatty acid, tricarboxylic acid cycle, and oxidative phosphorylation metabolite profiles that are characteristically disrupted in failing hearts. Genetic dependency experiments identified ERRgamma, not ERRalpha, as the primary mediator of cardioprotection in this model, with E2F1 pathway downregulation contributing to anti-proliferative effects.
This was published in Circulation, the highest-impact cardiovascular journal, reflecting peer recognition of the significance of the findings. However, the entire study is preclinical murine work.
The most clinically significant preclinical finding for SLU-PP-332. The Circulation publication and multi-omics characterization make this mechanistically credible. The ERRgamma dependence for cardiac protection is an important mechanistic clarification that distinguishes the cardiac application from the endurance application.
An 8-week protocol in aged mice reversed key markers of kidney aging: albuminuria was reduced, podocyte loss was attenuated, mitochondrial dysfunction was reversed, and inflammatory cytokine levels were normalized. The magnitude of benefit was compared to lifelong caloric restriction, the most validated intervention for aging-related kidney preservation, and ERR agonism produced comparable outcomes in aged animals without dietary modification.
The molecular mechanism involved the cGAS-STING pathway (a DNA-sensing innate immunity pathway that drives sterile inflammation in aging tissues) and STAT3 signaling. The study also showed that a STING inhibitor produced similar effects, confirming this pathway as a target of ERR agonism in kidney aging.
An independent commentary from a nephrology perspective noted SLU-PP-332's potential for indirect kidney protection through its metabolic effects on obesity and metabolic syndrome, which are major drivers of chronic kidney disease.
Strong mechanistic framing for a kidney aging application, and the caloric restriction comparator adds important context. Entirely preclinical in aged mice. The cGAS-STING mechanistic link opens a broader aging biology narrative but does not constitute human evidence.
This 2025 study from Policlinico Tor Vergata is notable as the only published research using human tissue, though it is an in vitro cell culture study, not a human in vivo trial. Myoblasts isolated from sedentary women showed higher NOX4 (oxidative stress marker) and lower SIRT1, PGC-1alpha, ERRalpha, and FNDC5 compared to active women, confirming a molecular signature of inactivity-related muscle aging.
When SLU-PP-332 was applied to myoblasts from inactive subjects, it reversed these alterations: NOX4 was downregulated, SIRT1, PGC-1alpha, ERRalpha, and FNDC5 were upregulated. Cytotoxicity (LDH release), oxidative stress (ROS production), and cellular senescence (SA-beta-galactosidase) were all reduced. Myotube formation was promoted, and Akt and Bcl-2 upregulation indicated suppression of apoptotic pathways.
While this involves human cells rather than animal cells, it is an ex vivo culture experiment, not a clinical trial. The biologically relevant question of whether these effects translate to human skeletal muscle in a living person receiving the compound remains entirely unanswered.
The most translationally interesting recent publication because it uses human muscle cells rather than rodent models. However, ex vivo cell culture is not a human clinical trial, and the activation of these pathways in isolated myoblasts does not confirm any therapeutic benefit in a living human. The lead researcher explicitly called for further studies.
As of March 2026, SLU-PP-332 has no registered clinical trials, no Investigational New Drug application on public record, and no published human pharmacokinetic or safety data. The compound remains classified as Preclinical in all drug development databases.
The community-reported oral dosing protocols (250 mcg to 1.5 mg daily) are derived by internet forum extrapolation from mouse IP data, not from any validated human pharmacokinetic modeling. Mouse IP dosing of 50 mg/kg twice daily corresponds to an animal receiving the equivalent of over a gram per day based on body weight, but human oral bioavailability, first-pass metabolism, and tissue distribution for SLU-PP-332 are all completely unknown.
Doping control researchers at the German Sport University Cologne published analytical methods for detecting SLU-PP-332 and its metabolites in 2026, developed specifically for anti-doping purposes. This demonstrates that WADA-affiliated laboratories are preparing for athlete misuse. The existence of detection methods does not imply any safety validation.
The principal investigator, Bahaa Elgendy, has co-founded Pelagos Pharmaceuticals with intent to develop next-generation ERR agonists, including CNS-penetrant variants. SLU-PP-332 itself appears to be positioned as a tool compound rather than a clinical development candidate, which partially explains the absence of formal IND-track development.
Nine published preclinical studies and zero human trials defines where SLU-PP-332 stands. The biohacker community is running an uncontrolled human experiment with a compound whose human pharmacokinetics, safety window, and appropriate dose are entirely unknown. The WADA ban reflects performance-enhancing potential but says nothing about safety in humans.
SLU-PP-332 is a research tool compound with no validated human dosing. All published studies use IP injection in mice at 25 to 50 mg/kg twice daily. Human oral bioavailability, appropriate dose, and safety window are unknown. Lowering the dose to micrograms for human use is community extrapolation, not pharmacologically validated. No clinical trials have been conducted or registered.
Closest comparator is 5-Amino-1MQ (another exercise-mimetic small molecule in this database). SLU-PP-332 targets nuclear receptor transcription (ERR pathway), while 5-Amino-1MQ inhibits the NNMT enzyme; both attempt to shift cellular metabolism toward fat oxidation via different mechanisms. GW501516 (Cardarine, not profiled) uses a related approach via PPARdelta, but was abandoned due to carcinogenicity in animals. SLU-PP-332 researchers explicitly designed away from PPARdelta to avoid that liability.
No human safety data exists for SLU-PP-332. The following observations come exclusively from animal studies, primarily 4 to 8-week mouse protocols using intraperitoneal administration.
Liver enzymes: Mild elevations in ALT and AST were observed in some mouse cohorts at 50 mg/kg twice daily for 28 days. These were not described as clinically significant in the primary publications, but the signal exists and warrants attention in any human study.
Lipid effects: Mixed findings across studies. In diet-induced obese mice, SLU-PP-332 reduced total cholesterol and triglycerides. In lean chow-fed mice, the lipid profile effects were less pronounced. Community reports suggest anecdotal HDL reduction, but this has no controlled study support.
Cardiac hypertrophy signal: ERRs are highly expressed in cardiac tissue, and sustained ERR activation raises a theoretical concern for pathological cardiac remodeling. The heart failure study explicitly found that SLU-PP-332 improved ejection fraction without affecting cardiac hypertrophy at the doses and duration studied, but this was a disease model rather than a healthy animal safety study. The cardiac risk at higher doses or longer durations in healthy subjects is not characterized.
Blood-brain barrier: SLU-PP-332 does not penetrate the CNS, which limits neurological off-target effects but also limits applicability to neurodegenerative conditions.
Compound source risk: No regulatory oversight governs research chemical suppliers. Purity, identity, and absence of toxic contaminants in commercially available SLU-PP-332 are not guaranteed by any government authority. Certificate of Analysis documentation from independent third-party labs is the minimum standard for any preclinical researcher.
Bottom line on safety: SLU-PP-332 is a research tool compound with an incomplete preclinical safety profile and no human data whatsoever. Its use outside a supervised research setting carries undefined risk.
SLU-PP-332 is the most credible exercise mimetic compound in the current research literature. The mechanistic case, the breadth of preclinical findings across muscle, metabolism, heart, and kidney, and the quality of the peer-reviewed publications, including a 2024 paper in Circulation, make it a serious scientific candidate for further development. This is not another noise compound.
However, the gap between preclinical promise and human applicability is wide. The entire evidence base is murine, and the only published work with human tissue is a cell culture experiment. Human oral pharmacokinetics are unknown. Safe and effective doses in people are unknown. The biohacker community has constructed an oral dosing protocol on zero validated data, working backward from mouse IP studies. That is not a reasonable basis for human self-experimentation.
The WADA prohibition is based on performance-enhancing potential, not safety. These are different questions. A compound can be banned for sport and simultaneously be insufficiently studied to know whether it is safe. SLU-PP-332 is currently both. If the Pelagos Pharmaceuticals development program produces a Phase 1 trial, this profile will update. Until then, the evidence tier is Tier 4 and the human risk profile is undefined.
For research and educational purposes only · Not medical advice · Consult a qualified physician before any human use