The Compound Report is an educational resource. Nothing on this site constitutes medical advice or encourages personal use of any compound. Always consult a qualified healthcare provider.
Educational reference only. Nothing on this page constitutes medical advice or encourages personal use of this compound. Always consult a qualified healthcare provider before any decision involving your health.
SLU-PP-332 is the most pharmacologically novel compound in this book and the one where the gap between scientific excitement and clinical readiness is most extreme. It does something no other compound here does: directly activates the transcriptional master switch of aerobic exercise. The biology is real. The translation to humans is a complete unknown.
The central tension resolved: A sedentary mouse given SLU-PP-332 runs 70% farther than an untreated sedentary mouse. This is a genuine and dramatic finding. The mechanism is confirmed, the ERRα specificity is proven, the gene expression signature is the aerobic exercise program. WADA banned it before a single human received it. Metabolite detection assays are in development. A Phase 1 trial has not been registered. The community is using it at doses potentially 3,500-12,000-fold below the animal study doses, via an oral route rather than intraperitoneal injection, with no pharmacokinetic reference for whether they are achieving any receptor activation at all, and no safety monitoring for the cardiac signal that the preclinical work identified. The 70% endurance figure is from mice. Whether any humans have experienced any endurance benefit at community doses is entirely unknown — the consistent self-reports of improved aerobic performance may reflect genuine ERR activation at sub-animal-study-doses, or they may reflect expectation effects in a highly motivated self-experimenting population, or some combination. There is no way to know without controlled data.
The strongest argument for SLU-PP-332: the mechanism is the most direct and complete exercise mimicry ever characterized pharmacologically. The target (ERRα) is the right target. The downstream biology is the right biology. The animal data is the most dramatic endurance enhancement in the exercise mimetic literature. The compound is orally bioavailable. If a Phase 1 trial establishes safety and a Phase 2 establishes that the gene expression findings translate to human endurance improvement — this would be one of the most significant metabolic therapeutic discoveries of the century.
The strongest argument for caution: every positive statement in the previous paragraph is conditional on human translation that has not occurred. The cardiac signal is uncharacterized in humans. The dose that produces any ERR activation in humans is unknown. The community is taking what may be pharmacologically inert doses of a compound for which no human reference data exists. The WADA ban is appropriate and the detection infrastructure is being built. Any legitimate therapeutic application is years away from approval even if Phase 1 goes perfectly.
Every time you go for a long run, your muscles send a signal. The mitochondria multiply. The oxidative fibers increase. The fat-burning enzymes upregulate. Your cardiovascular system adapts. This cascade of changes is not random — it is a coordinated genetic program, driven by a master transcriptional regulator called PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). PGC-1α doesn't act alone. It needs partners — nuclear receptor proteins that recruit it to the right genes at the right time. The estrogen-related receptors (ERRα, ERRβ, ERRγ) are among the most important of those partners. The question the researchers at St. Louis University asked was: what happens if you activate the ERRs directly with a synthetic agonist?
The estrogen-related receptors are orphan nuclear receptors — they were discovered through genetic similarity to estrogen receptors, but unlike estrogen receptors, no endogenous ligand has been clearly identified for them. ERRα in particular is a critical regulator of oxidative metabolism. Loss of ERRα function impairs mitochondrial oxidative capacity and reduces exercise endurance in animal models. Its activation is specifically required for the endurance component of exercise adaptation. This made ERRα an attractive drug target for exercise mimicry — if you could find a synthetic ligand that bound and activated ERRα, you might be able to trigger the aerobic exercise genetic program without the exercise.
Cyrielle Billon, Thomas Burris, and colleagues at Washington University in St. Louis identified SLU-PP-332 (CAS 303760-60-3) as a synthetic pan-agonist of all three ERRs — activating ERRα, ERRβ, and ERRγ with EC50 values of 98, 230, and 430 nM respectively. The highest potency is for ERRα at 98 nM — firmly in the nanomolar range that characterizes potent receptor agonists. The compound also had sufficient pharmacokinetic properties (oral bioavailability ~45% in rodents, half-life ~8-10 hours) to work as an in vivo tool — it could be given orally to animals and reach relevant concentrations.
The results published in ACS Chemical Biology (2023) were striking. Sedentary mice treated with SLU-PP-332 showed a 70% increase in treadmill running endurance compared to untreated controls. This was not a modest effect. The compound increased the proportion of type IIa oxidative muscle fibers — the slow-twitch, fatigue-resistant fibers that aerobic training develops. It induced the ERRα-specific acute aerobic exercise genetic program, confirmed by knocking out ERRα — in mice without ERRα, SLU-PP-332 lost its endurance-enhancing effect, proving the mechanism was specifically ERRα-dependent. And the compound had no obvious safety flags in the short-term animal studies.
The implications were immediate and obvious to the sports and anti-aging communities. A compound that activates the aerobic exercise genetic program, administered orally, increasing endurance by 70% in sedentary mice. This is the class of compound that WADA exists to prevent from entering competitive sport. The World Anti-Doping Agency added SLU-PP-332 to its 2025 Prohibited List under S4.4 Metabolic Modulators — effective January 1, 2025 — before any human trial had been conducted. The community was already using it before WADA banned it. They continued after.
THE CENTRAL TENSION — AND A STRUCTURAL CLARIFICATION
SLU-PP-332 is not a peptide. It has no amino acid sequence. It cannot be reconstituted from lyophilized powder in a bacteriostatic water vial. It is a synthetic small molecule — the same category as ibuprofen, metformin, or sildenafil. It is included in this book because the community discusses it in the same breath as MOTS-c, CJC-1295/Ipamorelin, and the other exercise-performance compounds covered here, and because its mechanism (ERR-mediated exercise mimicry) is directly relevant to the same biological questions. The central tension: a compound with the most dramatic endurance enhancement animal data of any exercise mimetic ever studied — 70% improvement in sedentary mice — with zero human trials, a WADA explicit ban on day one, and a community already using it orally from research chemical vendors without any pharmacokinetic data in humans. The biology is impressive. The human unknowns are total.
The animal evidence is the most dramatic of any exercise mimetic studied to date. The human evidence is zero. These are the complete bounds of what is known.
The defining result from Billon et al. 2023: sedentary mice treated with SLU-PP-332 showed a 70% increase in treadmill running endurance compared to untreated sedentary controls. This is not a modest improvement. For context, weeks of voluntary exercise training in mice typically produce 20-50% endurance improvements. SLU-PP-332 produced this pharmacologically, without any additional exercise, in sedentary animals. The mechanism was confirmed as ERRα-specific — knockout of ERRα abolished the endurance enhancement entirely. This specificity confirmation is important because it rules out off-target effects as the explanation. Grade C: dramatic, mechanism-confirmed animal finding; zero human endurance data. Whether this translates to a 70% endurance improvement in trained human athletes (who already have well-developed oxidative fiber profiles), untrained humans, or anywhere in between — is completely unknown.
A follow-up Billon et al. publication (Journal of Pharmacology and Experimental Therapeutics, 2023) studied SLU-PP-332 in a metabolic syndrome model — mice fed a high-fat diet to produce obesity, insulin resistance, and dyslipidemia. SLU-PP-332 treatment improved metabolic parameters: reduced adiposity, improved insulin sensitivity, reduced circulating triglycerides and cholesterol. The metabolic syndrome improvements are the most therapeutically compelling potential application for a human drug — this is a population with genuine unmet need who cannot or will not exercise adequately. Grade C: metabolic syndrome animal model; consistent with ERRα mechanism; not translated to human metabolic disease trial.
Wang et al. (American Journal of Pathology, 2023) [3] showed that ERR agonism with SLU-PP-332 ameliorated cardiac hypertrophy in a mouse model — reversed the pathological enlargement of the heart that occurs in response to pressure overload. The mechanism: ERRα activation in cardiac tissue restored mitochondrial oxidative metabolism in cardiac muscle that is impaired in hypertrophic hearts, reducing the energetic deficit that drives pathological remodeling. This is a potentially important therapeutic finding for heart failure. The tension: the same study noted heart rate changes with SLU-PP-332 treatment — a cardiovascular signal that requires characterization before human use. Grade C: cardiac hypertrophy reversal is promising; cardiac rate signal requires attention.
Billon et al. also showed SLU-PP-332 suppressed inflammatory myopathy in a mouse model of muscle inflammatory disease (Journal of Pharmacology and Experimental Therapeutics, 2023). ERRα activation in this context appeared to shift the muscle inflammatory microenvironment toward resolution. Grade C: animal model; relevant for conditions like polymyositis or dermatomyositis; not a primary community application.
Bonanni et al. (Frontiers in Physiology, 2025) [5] reviewed ERR targeting specifically for age-related muscle atrophy (sarcopenia). ERRα activation's promotion of oxidative fiber maintenance and mitochondrial biogenesis is directly mechanistically relevant to the age-related loss of Type I and IIa fibers and mitochondrial density that drives sarcopenia. Grade C: mechanistic review plus supporting animal data; sarcopenia application not directly trialed with SLU-PP-332 specifically.
Nasri (Journal of Renal Endocrinology, 2024) proposed SLU-PP-332 as a potential kidney-protective agent based on the ERR-mediated metabolic improvements reducing the chronic low-grade inflammation and mitochondrial dysfunction associated with kidney disease progression. Grade D: mechanistic proposal; no direct kidney model study with SLU-PP-332 published.
SLU-PP-332 has a molecular weight of approximately 384 Da — comparable to many peptides in this book in size, but fundamentally different in structure. It is a synthetic organic small molecule: a defined chemical compound with a fixed molecular structure built from organic chemistry, not amino acids. It has no peptide bonds. It has no N-terminus or C-terminus. It is synthesized through organic chemistry routes, not solid-phase peptide synthesis. This distinction matters practically for multiple reasons: small molecules typically have better oral bioavailability than peptides (because they resist GI proteolysis that destroys peptides); they have different regulatory pathways; and they have different quality control requirements.
SLU-PP-332's chemical structure features a phenol amide core that interacts with the ERR receptor binding pocket. The compound was designed from structure-activity relationship studies of ERR agonists, optimizing both receptor affinity and pharmacokinetic properties. The CAS number 303760-60-3 is the definitive identifier. Unlike peptides where mass spectrometry identity confirmation requires confirming the amino acid sequence mass, SLU-PP-332 identity is confirmed by its molecular weight (~384 Da) and ideally by additional structural characterization (NMR, HPLC).
DO NOT INJECT THIS COMPOUND
Research chemical SLU-PP-332 oral solutions are dissolved in PEG, ethanol, DMSO, or similar solvents. These formulations are NOT sterile, NOT endotoxin-tested, and NOT formulated for injection. DMSO in particular is highly tissue-toxic if injected. The oral route is appropriate for SLU-PP-332 given its ~45% oral bioavailability. Injecting it is both unnecessary and dangerous. This is fundamentally different from the SubQ-injectable peptides throughout this book.
Published rodent pharmacokinetic data: oral bioavailability approximately 45% — significantly better than most peptides in this book, which have negligible oral bioavailability. Plasma half-life approximately 8-10 hours in rodents, suggesting twice-daily dosing to maintain steady-state concentrations. The compound is cleared primarily hepatically. Mouse studies used intraperitoneal injection at 50 mg/kg; human-equivalent oral doses are dramatically lower given the different route, species allometry, and bioavailability. All rodent PK figures are from the original Billon 2023 [1] research. No human pharmacokinetic study has been published.
Billon et al. published SLU-PP-915 in the Journal of Pharmacology and Experimental Therapeutics (2026) — a next-generation ERR agonist from the same Washington University research group, specifically designed for improved potency, ERRα selectivity, and oral bioavailability. SLU-PP-915 demonstrated enhanced aerobic exercise capacity in the published study. The existence of SLU-PP-915 signals the direction of the field: SLU-PP-332 was the proof-of-concept compound; the next generation is already characterized. Community members tracking this space should monitor SLU-PP-915 development as it represents the likely next chapter in ERR agonist evolution.
SLU-PP-332's mechanism is elegant and well-characterized at the molecular level. It activates nuclear receptors that are the master switches of aerobic metabolism. The downstream biology is the gene expression program of endurance exercise. No other mechanism in this book more directly mimics a specific physiological process at the transcriptional level.
ERRα (estrogen-related receptor alpha) is a nuclear transcription factor that controls the expression of hundreds of genes involved in oxidative phosphorylation, fatty acid oxidation, mitochondrial biogenesis, and electron transport. It is one of the most important regulators of the aerobic metabolic phenotype — the cluster of adaptations that make a cell or tissue better at sustained aerobic energy production. ERRα activity increases during exercise and is upregulated by physical training over time. Loss of ERRα (ERRα knockout mice) impairs oxidative fiber content and reduces exercise endurance. This is the pharmacological rationale: activating ERRα pharmacologically should produce the same gene expression changes that exercise training produces. Grade A for ERRα's role in exercise adaptation (very well-established exercise physiology). Grade C for SLU-PP-332's specific effects (animal models only; mechanism confirmed but human translation unvalidated).
PGC-1α is the transcriptional coactivator that orchestrates the full aerobic exercise adaptation program — it is recruited to gene promoters by ERRα and other nuclear receptors to drive expression of mitochondrial genes. When SLU-PP-332 activates ERRα, ERRα recruits PGC-1α to the promoters of genes encoding mitochondrial respiratory complexes, fatty acid oxidation enzymes, and fiber-type specification factors. The result is upregulation of the same gene expression program that weeks of aerobic training produce — but in a single pharmacological dose. The Billon 2023 [2] paper specifically confirmed this by transcriptomically profiling SLU-PP-332-treated muscle cells and showing the exercise genetic signature. Grade C: animal and cell culture; mechanism confirmed; human muscle response not characterized.
Skeletal muscle fibers come in types determined by their metabolic profile. Type I (slow-twitch, oxidative) and Type IIa (fast-twitch oxidative) are fatigue-resistant and depend on aerobic metabolism. Type IIb (fast-twitch glycolytic) fatigue quickly and depend on anaerobic glycolysis. Aerobic training increases the proportion of Type IIa fibers relative to Type IIb — a key adaptation for endurance. SLU-PP-332 treatment in mice increased the proportion of Type IIa oxidative fibers, providing a structural muscular adaptation consistent with the exercise phenotype. This fiber-type shift is one of the most mechanistically coherent findings — it directly explains the enhanced endurance via a measurable structural change in muscle. Grade C: animal histology; consistent with ERRα mechanism; not demonstrated in human biopsy.
The Billon 2023 paper identified that SLU-PP-332 induces expression of DDIT4 (DNA Damage Inducible Transcript 4, also known as REDD1) as part of the acute aerobic exercise genetic response. DDIT4 is upregulated during acute exercise and is an mTOR regulator. Its induction by SLU-PP-332 provided a molecular marker of the exercise mimetic response and was used to confirm ERRα specificity — DDIT4 induction was abolished in ERRα knockout mice. Grade C: molecular marker confirmation; animal-only.
Exercise increases heart rate and cardiac output. A compound that mimics the gene expression of exercise raises the question: does it also affect cardiac function? Published animal studies and community reports suggest SLU-PP-332 may produce heart rate elevation at higher doses — a plausible consequence of ERR activation in cardiac tissue, where ERRs also regulate metabolic gene expression. The cardiac signal in preclinical studies has been cited as one of the key concerns for the Phase 1 trial design — cardiovascular telemetry monitoring is expected to be a central component of any first-in-human study. The specific magnitude and clinical significance of cardiac effects in humans is unknown. Grade C: animal signal; specific human cardiovascular risk not characterized.
MECHANISM SUMMARY — WHAT MAKES THIS DIFFERENT
SLU-PP-332 activates the transcriptional master switches of aerobic adaptation. The downstream effects are the genetic program of exercise, not a pharmacological substitute for exercise's individual molecular events. MOTS-c (covered in this book) also activates AMPK and produces some exercise-mimetic effects — but via a metabolic signaling cascade. SLU-PP-332 works at the nuclear receptor level, directly reprogramming gene expression in a way that parallels aerobic training more comprehensively than AMPK activation alone. This is why the endurance enhancement in mice (70%) is so much larger than what MOTS-c produces. It is also why WADA treated it with such seriousness — the transcriptional scope of ERR activation is broader and more fundamental than any other exercise mimetic mechanism currently known.
SLU-PP-332 has the most direct and most comprehensively characterized gene expression mechanism of any compound in this book. Unlike compounds that activate cell-surface receptors and produce downstream signaling cascades that eventually affect gene expression (MOTS-c via AMPK/PGC-1α, SS-31 via cardiolipin stabilization → secondary transcriptional effects), SLU-PP-332 acts directly as a nuclear receptor agonist — it binds inside cells to the ERRs themselves and directly changes what those transcription factors do. The transcriptomic signature produced by SLU-PP-332 treatment in skeletal muscle cells mirrors the acute aerobic exercise transcriptome — the specific pattern of gene expression changes that occurs during and immediately after exercise. This was not inferred; it was demonstrated by direct transcriptomic comparison in the Billon 2023 study. Upregulated genes include those encoding: Complex I-V subunits of the mitochondrial respiratory chain; fatty acid oxidation enzymes (ACADL, HADHA, HADHB); fiber-type specification factors; PGC-1α co-regulatory networks; and DDIT4 (the exercise-responsive gene used as a mechanistic marker). Downregulated: glycolytic enzyme dependence in slow-twitch fiber contexts. This is not a partial overlap with exercise gene expression — the paper describes it as an ERRα-specific acute aerobic exercise genetic program. No other compound in this book has this level of transcriptional specificity for exercise adaptation.
THE COMPLETE HUMAN EVIDENCE FOR SLU-PP-332
There is no human evidence. Not thin evidence. Not contested evidence. None. No Phase 1 trial. No registered clinical trial on ClinicalTrials.gov. No open-label human study. No pharmacokinetic study in humans. No safety study in humans. No efficacy study in humans. The entire evidence base consists of animal studies and cell culture work — compelling, well-designed, and published in peer-reviewed journals by legitimate researchers — but not a single data point from a human subject. The community using this compound is conducting an uncontrolled first-in-human experiment with no reference point for appropriate dose, safety margin, cardiac risk, or any other pharmacological parameter in the human context.
Application
Model
Grade
Key Finding
Human Translation
Endurance enhancement
Sedentary mice, treadmill test
C
70% endurance increase; ERRα-specific; Type IIa fiber increase
Unknown — may be largest effect in sedentary/metabolically impaired; unknown in trained individuals
Metabolic syndrome
High-fat diet mice
C
Reduced adiposity, improved insulin sensitivity, lipid normalization
Unknown — most therapeutically compelling for human drug development
Cardiac hypertrophy reversal
Pressure overload mouse model
C
Restored cardiac mitochondrial metabolism; reversed pathological hypertrophy
Unknown — cardiac signal also observed; requires careful monitoring
Inflammatory myopathy
Mouse myopathy model
C
Suppressed muscle inflammation
Unknown — potential for inflammatory muscle diseases
Sarcopenia / aging muscle
Review + animal data
C
ERRα activation maintains oxidative fibers; directly relevant mechanism
Unknown — no human trial
Kidney protection
Mechanistic proposal
D
Theoretical based on metabolic improvements
Speculative
Human safety at any dose
None
X
Not studied
Not established
| Application | Evidence level | Grade | Confidence | Key limitation |
|---|---|---|---|---|
| Endurance enhancement | Sedentary mice, treadmill test | C | 70% endurance increase; ERRα-specific; Type IIa fiber increase | Unknown — may be largest effect in sedentary/metabolically impaired; unknown in trained individuals |
| Metabolic syndrome | High-fat diet mice | C | Reduced adiposity, improved insulin sensitivity, lipid normalization | Unknown — most therapeutically compelling for human drug development |
| Cardiac hypertrophy reversal | Pressure overload mouse model | C | Restored cardiac mitochondrial metabolism; reversed pathological hypertrophy | Unknown — cardiac signal also observed; requires careful monitoring |
| Inflammatory myopathy | Mouse myopathy model | C | Suppressed muscle inflammation | Unknown — potential for inflammatory muscle diseases |
| Sarcopenia / aging muscle | Review + animal data | C | ERRα activation maintains oxidative fibers; directly relevant mechanism | Unknown — no human trial |
| Kidney protection | Mechanistic proposal | D | Theoretical based on metabolic improvements | Speculative |
| Human safety at any dose | None | X | Not studied | Not established |
CRITICAL DOSING DISCLAIMER — ESPECIALLY SERIOUS FOR THIS COMPOUND
SLU-PP-332 has no validated human dose. No Phase 1 dose-escalation study exists. No human pharmacokinetic study exists. Community dosing is derived from rodent study concentrations scaled by rough allometric factors — a method known to fail for many small molecules due to species-specific differences in metabolism, receptor pharmacology, and tissue distribution. The mouse studies that generated the 70% endurance finding used intraperitoneal injection at 50 mg/kg. The allometrically scaled human oral-equivalent dose (accounting for IP vs oral bioavailability and species differences) would be in the range of hundreds of milligrams — far above the 0.25-1 mg community doses. Whether the community doses produce any meaningful ERR activation in humans, or whether they are simply below any pharmacologically active threshold, is genuinely unknown.
Unlike every other compound in this book, SLU-PP-332 does not require subcutaneous injection. Its ~45% oral bioavailability in rodents — exceptional for this class of compound — is what makes it drug-development-relevant. The oral route is pharmacologically appropriate, practically convenient, and aligns with the research formulations. Community users take it orally. Research vendors supply it as oral liquids or capsules. Do not attempt to inject research-grade SLU-PP-332 preparations.
Protocol
Dose
Timing
Frequency
Notes
Conservative / entry
250 mcg (0.25 mg)
Morning with food
Daily
Far below any animal study dose; may be sub-threshold in humans
Standard community
500 mcg (0.5 mg)
Split AM/midday
Twice daily
Most common reported protocol; accounts for ~8-10hr rodent half-life
Higher community
1,000 mcg (1 mg)
Split AM/midday
Twice daily
Upper end of reported community range; cardiac monitoring warranted
Mouse study reference (IP)
50 mg/kg IP
Single or multiple
Daily/every other day
The dose that produced 70% endurance increase; not comparable to human oral use
The dose gap between the mouse study (50 mg/kg IP) and community use (0.25-1 mg oral, equivalent to ~0.004-0.014 mg/kg for a 70 kg adult) is approximately 3,500-12,000-fold. Even accounting for IP vs oral bioavailability (~45%), allometric scaling (mice to humans requires dose reduction per the standard 12.3 conversion factor), and other species differences — the community doses are likely substantially below the pharmacologically effective doses shown in animal models. Whether sub-threshold doses produce any benefit, or whether they simply do nothing, is the first question a Phase 1 pharmacodynamic study would answer. The community does not have this answer.
Research-grade SLU-PP-332 oral solutions are typically dissolved in polyethylene glycol 400 (PEG-400), or PEG/ethanol blends, at concentrations of 1-10 mg/mL. These are not sterile pharmaceutical preparations. Shake before use to ensure uniform suspension. Store according to vendor instructions — typically refrigerated or room temperature, away from light, for up to 3-6 months (small molecule stability is generally better than reconstituted peptides). COA requirements: HPLC purity 98%+ minimum; HNMR or mass spectrometry confirming ~384 Da identity. Pricing 2026: research vendor (HPLC + purity documentation), 50 mg SLU-PP-332 in oral solution: $40-90.
The ~8-10 hour rodent half-life suggests twice-daily dosing to maintain reasonable steady-state concentrations — though this may not apply to human pharmacokinetics. The community standard is morning and midday dosing. Unlike Semax, there is no specific stimulatory or sleep-disruption concern documented for SLU-PP-332 that would make evening dosing problematic — but given the cardiac signal at higher doses, avoiding late evening dosing when cardiovascular monitoring is not available is prudent.
Given the cardiac signal observed in animal studies, any user of SLU-PP-332 should at minimum: (1) establish resting heart rate baseline before starting; (2) monitor resting heart rate daily during use; (3) note any palpitations, chest discomfort, or unusual shortness of breath and discontinue immediately. Blood pressure monitoring is also reasonable. These are not guaranteed to catch all adverse cardiac events, but they provide a basic signal. The Phase 1 trial design for SLU-PP-332 will almost certainly include cardiac telemetry and echocardiography — the absence of this monitoring in community use is a real gap.
The published animal studies report SLU-PP-332 as generally well-tolerated in the models studied. No hepatotoxicity, nephrotoxicity, or severe organ damage was observed in the studies published through 2026. The cardiac signal — heart rate elevation at higher doses — is the primary safety concern identified in preclinical work. This is not a documented human adverse effect because no human study exists. The absence of reported harm in animal models does not constitute a safety clearance for human use, particularly for a compound that activates nuclear receptors with broad transcriptional effects across multiple organ systems.
CARDIAC MONITORING IS NOT OPTIONAL
Exercise increases heart rate. A compound that mimics exercise gene expression may also affect cardiac function. Animal studies identified heart rate changes with SLU-PP-332 at higher doses. This signal is precisely why cardiovascular telemetry is expected to be a central component of the Phase 1 trial design. For community users with: hypertension; any known cardiovascular disease; arrhythmia history; or structural cardiac abnormalities — SLU-PP-332 is contraindicated until human cardiac safety data exists. For any user: monitor resting heart rate before, during, and after cycles. Discontinue if heart rate elevation, palpitations, or chest symptoms occur.
SLU-PP-332 is an estrogen-related receptor agonist, not an estrogen receptor agonist. ERRs share sequence similarity with the classical estrogen receptors (ERα and ERβ) but have different structures, different endogenous ligands (none clearly identified for ERRs), and completely different pharmacology. SLU-PP-332 does not bind or activate estrogen receptors. It does not produce estrogenic effects, feminizing effects, or HPTA suppression. This confusion appears in community forums and is consistently incorrect. The 'estrogen-related' in the receptor name refers to sequence similarity, not functional equivalence.
WADA BAN AND METABOLITE DETECTION — THE COMPLETE PICTURE
The WADA ban is explicit and effective as of January 1, 2025. More significantly for athletes considering use: the Avliyakulov et al. 2026 publication identified 22 SLU-PP-332 metabolites specifically for doping control purposes. This paper was published by anti-doping researchers to enable development of detection assays. If detection tests for SLU-PP-332 do not yet exist in all testing programs, they will. The window of undetectable use — if it ever existed — is closing. Athletes subject to WADA testing should treat SLU-PP-332 as both prohibited and soon-to-be detectable.
SLU-PP-332 activates the aerobic exercise gene program at the nuclear receptor level. This is mechanistically distinct from — and potentially complementary to — every other compound in this book. Its stacking logic is entirely different from peptide stacks.
MOTS-c activates AMPK via folate cycle inhibition, producing metabolic signaling that partially mimics exercise. SLU-PP-332 activates ERRα/PGC-1α, producing the transcriptional gene program of exercise. These are different layers of the same ultimate biological outcome — exercise adaptation. AMPK activation (MOTS-c) is a metabolic sensor response; ERR activation (SLU-PP-332) is a transcriptional programming response. The two mechanisms are non-redundant and potentially synergistic: MOTS-c provides the acute metabolic signaling that exercise produces; SLU-PP-332 provides the gene expression changes that sustained training produces. Both WADA S4.4 banned. Athletes cannot use either; non-competitive users theoretically have the most comprehensive exercise-mimetic stack available.
GH secretagogues provide anabolic support (protein synthesis, tissue repair, sleep quality) through the GH/IGF-1 axis. SLU-PP-332 provides the aerobic metabolic gene program through ERR activation. These are entirely different mechanisms addressing different aspects of physical performance — aerobic capacity and endurance (SLU-PP-332) versus body composition and recovery (GH secretagogues). Non-overlapping axes. Both WADA banned.
Beta-blockers, calcium channel blockers, and other heart rate-modifying medications may mask or interact with the cardiac effects of SLU-PP-332. Anyone on cardiovascular medications should not use SLU-PP-332 without physician oversight. SLU-PP-332's cardiac effects may interact unpredictably with antiarrhythmic medications.
This is not a theoretical stack — it is the most important combination context for this compound. SLU-PP-332 activates the gene program of aerobic exercise. Actual aerobic exercise provides the mechanical, neurological, hormonal, and cardiovascular stimuli that exercise produces. The combination of ERR activation (gene program) with real exercise (full physiological stimulus) is the context most likely to produce additive or synergistic benefit — the genetic program is activated, and the physical stimulus gives it something meaningful to respond to. Community users who report the most consistent effects with SLU-PP-332 are generally those who combine it with regular training, not those who use it as a sedentary substitute.
Improved endurance and reduced perceived effort during cardiovascular exercise is the most commonly reported early effect. Some users report feeling warmer or having increased resting energy expenditure. Heart rate monitoring is appropriate starting from day 1.
Sustained aerobic performance improvements. Some users report subjective fat loss or body composition changes. The community's most consistently reported benefit: aerobic exercise feels easier and performance improves noticeably relative to baseline.
Peak reported benefit window for most users. Continued endurance improvement. Some bloodwork reporters note metabolic marker improvements (fasting glucose, triglycerides) in this window, consistent with the animal metabolic syndrome data.
Effects appear to diminish over weeks after stopping, suggesting the gene expression changes require ongoing compound presence — consistent with nuclear receptor pharmacology where effects persist only with continued agonist exposure.
Because no human trial exists, the following is entirely from community self-reports.
Timeframe
Community-Reported (Grade E)
Days 1-5
Improved endurance and reduced perceived effort during cardiovascular exercise is the most commonly reported early effect. Some users report feeling warmer or having increased resting energy expenditure. Heart rate monitoring is appropriate starting from day 1.
Week 1-2
Sustained aerobic performance improvements. Some users report subjective fat loss or body composition changes. The community's most consistently reported benefit: aerobic exercise feels easier and performance improves noticeably relative to baseline.
Week 2-4
Peak reported benefit window for most users. Continued endurance improvement. Some bloodwork reporters note metabolic marker improvements (fasting glucose, triglycerides) in this window, consistent with the animal metabolic syndrome data.
Post-cycle
Effects appear to diminish over weeks after stopping, suggesting the gene expression changes require ongoing compound presence — consistent with nuclear receptor pharmacology where effects persist only with continued agonist exposure.
The most important practical question for any community user is whether their dose is even producing ERR activation. Given the extreme dose gap between animal study protocols and community dosing — potentially 3,500-12,000-fold lower — the pharmacodynamic question is: are community doses above the minimum effective concentration in humans for any receptor activation? Some community users report clear effects. Some report nothing. This distribution is consistent with two possible explanations: genuine dose-response variation between individuals, OR some users happen to be taking amounts that hit threshold while most take amounts that don't. There is no way to distinguish these explanations without human PK/PD data.
No established cycling protocol — no clinical data to derive one from. Community practice: 4-8 week on cycles with 2-4 week breaks. The nuclear receptor mechanism (ongoing agonist activation required for continued gene expression effects) suggests that taking breaks reduces the cumulative exposure while allowing assessment of baseline vs on-compound performance. Whether receptor downregulation or tolerance develops with continuous use is unknown.
SLU-PP-332 entered community use significantly before the WADA ban — primarily through the biohacking and performance optimization communities. Post-ban, non-competitive users (recreational athletes, longevity-focused users, metabolically impaired individuals seeking exercise mimicry) represent the primary community. Competitive athletes who continue to use it are taking a knowing and documented doping violation risk. The community consensus is most consistent for aerobic performance improvement with concurrent exercise — the 'easier cardio' report is the most common benefit description. Community metabolic users (metabolic syndrome, T2D interest) are a growing but smaller segment. The compound's community profile is distinctly different from most peptides in this book: users tend to be more performance-focused than longevity-focused, and the discourse is more sophisticated about the animal-to-human translation question than for most research chemicals.
The open question list for SLU-PP-332 is essentially the entire human pharmacology of the compound.
The honest position on SLU-PP-332 in 2026: the most pharmacologically impressive exercise mimetic compound identified to date, with the most dramatic animal endurance data, the most mechanistically precise target (ERRα), and zero human pharmacology data of any kind. WADA understood the performance enhancement implications well enough to ban it before any human tested it. The community is conducting an unprecedented self-experiment in exercise pharmacology with no dosing reference, no safety data, no efficacy floor, and a cardiac signal that demands clinical monitoring that most users aren't getting.
Research provenance: SLU-PP-332 research is concentrated at Washington University in St. Louis (Billon, Burris group) with growing independent academic interest. Multiple published studies across ACS Chemical Biology, Journal of Pharmacology and Experimental Therapeutics, and American Journal of Pathology. The anti-doping detection work (Avliyakulov 2026) comes from independent doping control researchers. Provenance is significantly better than many compounds in this book — multiple peer-reviewed publications from the original academic group with growing independent citations.
Billon C, Sitaula S, Banerjee S, et al. (2023). Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chemical Biology. 18(4):756-771. PMC11584170. doi:10.1021/acschembio.2c00720. [THE foundational paper: SLU-PP-332 characterized; 70% endurance increase in sedentary mice; ERRα-specific mechanism confirmed by knockout; Type IIa fiber increase; transcriptomic exercise gene signature. Washington University.]
Billon C, et al. (2023). Synthetic ERR Agonist Increases Exercise Endurance and Suppresses Inflammatory Myopathy in Skeletal Muscle. Journal of Pharmacology and Experimental Therapeutics. PMID 37739806. [Metabolic syndrome alleviation + inflammatory myopathy suppression; Washington University]
Wang XX, et al. (2023). ERR Agonist SLU-PP-332 Ameliorates Cardiac Hypertrophy. American Journal of Pathology. doi:10.1016/j.ajpath.2023.03.021. [Cardiac hypertrophy reversal; ERR activation in cardiac tissue; heart rate signal documented; Washington University + collaborators]
Billon C, Appourchaux K, Côté I, Burris TP. (2026) [4]. An orally active estrogen receptor–related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. Journal of Pharmacology and Experimental Therapeutics. 393(1):103787. doi:10.1016/j.jpet.2025.103787. [SLU-PP-915 successor compound: more potent, better ERRα selectivity, improved oral bioavailability; the next chapter in this research program]
Bonanni R, et al. (2025). Targeting ERRs to Counteract Age-Related Muscle Atrophy. Frontiers in Physiology. doi:10.3389/fphys.2025.1616693. [ERR targeting for sarcopenia review; mechanistic relevance for aging muscle; independent Italian group]
Avliyakulov NK, Sobolevsky T, Ahrens E. (2026). Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes. Drug Testing and Analysis. doi:10.1002/dta.70035. [22 metabolites identified for doping control; confirms WADA 2025 Prohibited List listing; detection assay development in progress]
Eissa I. (2025) [7]. SLU-PP-332 and Related ERRα Agonists: A Focused Minireview of Metabolic Regulation and Therapeutic Potential. Universal Journal of Pharmaceutical Research. 10(3). [Independent review; comprehensive summary of mechanism and applications through 2025]
WADA. (2025). 2025 Prohibited List. S4.4 Metabolic Modulators — Activators of the AMP-activated protein kinase (AMPK) [covers MOTS-c] AND metabolic modulators including ERR agonists [covers SLU-PP-332]. Effective January 1, 2025. [Confirmed via Avliyakulov 2026 citation of the 2025 list document]
SLU-PP-332 is the most pharmacologically novel compound in this book and the one where the gap between scientific excitement and clinical readiness is most extreme. It does something no other compound here does: directly activates the transcriptional master switch of aerobic exercise. The biology is real. The translation to humans is a complete unknown.
The central tension resolved: A sedentary mouse given SLU-PP-332 runs 70% farther than an untreated sedentary mouse. This is a genuine and dramatic finding. The mechanism is confirmed, the ERRα specificity is proven, the gene expression signature is the aerobic exercise program. WADA banned it before a single human received it. Metabolite detection assays are in development. A Phase 1 trial has not been registered. The community is using it at doses potentially 3,500-12,000-fold below the animal study doses, via an oral route rather than intraperitoneal injection, with no pharmacokinetic reference for whether they are achieving any receptor activation at all, and no safety monitoring for the cardiac signal that the preclinical work identified. The 70% endurance figure is from mice. Whether any humans have experienced any endurance benefit at community doses is entirely unknown — the consistent self-reports of improved aerobic performance may reflect genuine ERR activation at sub-animal-study-doses, or they may reflect expectation effects in a highly motivated self-experimenting population, or some combination. There is no way to know without controlled data.
The strongest argument for SLU-PP-332: the mechanism is the most direct and complete exercise mimicry ever characterized pharmacologically. The target (ERRα) is the right target. The downstream biology is the right biology. The animal data is the most dramatic endurance enhancement in the exercise mimetic literature. The compound is orally bioavailable. If a Phase 1 trial establishes safety and a Phase 2 establishes that the gene expression findings translate to human endurance improvement — this would be one of the most significant metabolic therapeutic discoveries of the century.
The strongest argument for caution: every positive statement in the previous paragraph is conditional on human translation that has not occurred. The cardiac signal is uncharacterized in humans. The dose that produces any ERR activation in humans is unknown. The community is taking what may be pharmacologically inert doses of a compound for which no human reference data exists. The WADA ban is appropriate and the detection infrastructure is being built. Any legitimate therapeutic application is years away from approval even if Phase 1 goes perfectly.
SLU-PP-332 is the most pharmacologically novel compound in this book and the one where the gap between scientific excitement and clinical readiness is most extreme. It does something no other compound here does: directly activates the transcriptional master switch of aerobic exercise. The biology is real. The translation to humans is a complete unknown.
The central tension resolved: A sedentary mouse given SLU-PP-332 runs 70% farther than an untreated sedentary mouse. This is a genuine and dramatic finding. The mechanism is confirmed, the ERRα specificity is proven, the gene expression signature is the aerobic exercise program. WADA banned it before a single human received it. Metabolite detection assays are in development. A Phase 1 trial has not been registered. The community is using it at doses potentially 3,500-12,000-fold below the animal study doses, via an oral route rather than intraperitoneal injection, with no pharmacokinetic reference for whether they are achieving any receptor activation at all, and no safety monitoring for the cardiac signal that the preclinical work identified. The 70% endurance figure is from mice. Whether any humans have experienced any endurance benefit at community doses is entirely unknown — the consistent self-reports of improved aerobic performance may reflect genuine ERR activation at sub-animal-study-doses, or they may reflect expectation effects in a highly motivated self-experimenting population, or some combination. There is no way to know without controlled data.
The strongest argument for SLU-PP-332: the mechanism is the most direct and complete exercise mimicry ever characterized pharmacologically. The target (ERRα) is the right target. The downstream biology is the right biology. The animal data is the most dramatic endurance enhancement in the exercise mimetic literature. The compound is orally bioavailable. If a Phase 1 trial establishes safety and a Phase 2 establishes that the gene expression findings translate to human endurance improvement — this would be one of the most significant metabolic therapeutic discoveries of the century.
The strongest argument for caution: every positive statement in the previous paragraph is conditional on human translation that has not occurred. The cardiac signal is uncharacterized in humans. The dose that produces any ERR activation in humans is unknown. The community is taking what may be pharmacologically inert doses of a compound for which no human reference data exists. The WADA ban is appropriate and the detection infrastructure is being built. Any legitimate therapeutic application is years away from approval even if Phase 1 goes perfectly.
Well-suited for, if anyone: non-competitive adults with metabolic syndrome, obesity, or exercise limitation who have exhausted conventional interventions and are aware they are taking a research chemical with zero human safety data; longevity-focused users who understand the animal-to-human translation gap and accept that they may be taking sub-effective doses with unknown risks.
Not appropriate for: any competitive athlete under WADA, NCAA, USADA, or equivalent testing (explicit S4.4 ban, detection methodology in development); anyone with cardiovascular disease, hypertension, or arrhythmia history (cardiac signal requires human characterization first); anyone expecting the 70% endurance gain from sedentary mice to translate directly to their experience as an already-trained human.
Feature
SLU-PP-332
MOTS-c
Compound type
Small molecule (not a peptide)
Peptide (16 amino acids)
Target
ERRα/β/γ nuclear receptors (transcriptional)
AMPK (metabolic signaling) via AICAR
Mechanism specificity
Entire aerobic exercise transcriptional program
Metabolic signaling and AMPK pathway
Route
Oral (preferred); ~45% rodent bioavailability
SubQ injection
Animal endurance data
70% increase in sedentary mice (Billon 2023)
Improved in aged mice (Reynolds 2021)
Human data
Zero — no trial
Zero interventional — observational only
WADA status
S4.4 banned (explicit, since Jan 2025)
S4.4 banned (explicit)
Cardiac signal
Yes — heart rate elevation in animals
Not documented
Clinical development
No Phase 1 registered
No Phase 1 registered
Successor compound
SLU-PP-915 (JPET 2026)
None currently
— End of SLU-PP-332 —
THE PEPTIDE BIBLE | SLU-PP-332 | For Research & Educational Purposes Only
SLU-PP-332 is a synthetic small molecule ERRα/β/γ pan-agonist (NOT a peptide), molecular weight ~384 Da, CAS 303760-60-3, developed by Cyrielle Billon, Thomas Burris, and colleagues at Washington University in St. Louis. It is the most potent and mechanistically specific exercise mimetic identified to date. Primary mechanism: agonism of all three estrogen-related receptors (ERRα EC50 = 98 nM; ERRβ = 230 nM; ERRγ = 430 nM) with highest potency for ERRα. ERRα is the master transcriptional regulator of aerobic oxidative metabolism. Its activation drives PGC-1α co-regulatory networks, upregulating the complete gene expression program of aerobic exercise — mitochondrial biogenesis, fatty acid oxidation, Type IIa oxidative fiber specification. Foundational evidence: Billon et al. (ACS Chemical Biology, 2023): sedentary mice showed 70% endurance increase; ERRα-specificity confirmed by knockout; Type IIa fiber increase demonstrated; acute aerobic exercise transcriptional program induced. Subsequent studies: metabolic syndrome alleviation (Billon 2023, JPET), cardiac hypertrophy reversal (Wang 2023, AJP), inflammatory myopathy suppression. SLU-PP-915 (Billon 2026, JPET): next-generation successor compound with improved potency and selectivity. Human evidence: zero — no Phase 1 trial registered. Oral bioavailability ~45% in rodents; half-life ~8-10 hours (rodent). Community dosing: 0.25-1 mg/day oral, twice-daily. Community doses are potentially 3,500-12,000-fold below animal study doses — whether they produce any ERR activation in humans is unknown. Safety: cardiac heart rate signal in animals is primary concern; no human safety data. Route: ORAL ONLY — not formulated for injection; do not inject. WADA: explicitly banned S4.4 Metabolic Modulators since January 1, 2025; metabolite detection assays in active development (Avliyakulov 2026, Drug Testing and Analysis). FDA: no approval, no IND registered, research chemical only. The central tension: the most impressive exercise mimetic data in the published literature — zero human trial data — WADA banned before any human was studied — community already using it. The 70% sedentary mouse endurance figure and the zero human data point must be held simultaneously.