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SLU-PP-332

A pan-estrogen-related-receptor agonist that reproduces several endurance-training adaptations in mouse muscle without the training - the current front-runner for 'exercise in a bottle'.

Also known as pan-ERR agonist, exercise mimetic, SLU-PP-332

Animal data only — Rodent or other animal studies. Dose translation to humans is genuinely uncertain.

Genuinely promising mouse data from the Burris laboratory across endurance, obesity and heart failure models. There has never been a human trial, human pharmacokinetics are unknown, and it has already been flagged in the anti-doping literature as a compound with doping potential. Anyone quoting a human dose is guessing.

How it works

The estrogen-related receptors are orphan nuclear receptors that, with PGC-1alpha, run the transcriptional programme for oxidative metabolism - mitochondrial biogenesis, fatty acid oxidation, and the conversion of muscle toward slow, fatigue-resistant type I fibres. Endurance training works largely through this axis. SLU-PP-332 is a synthetic agonist with EC50 values around 98 nM at ERRalpha, 230 nM at ERRbeta and 430 nM at ERRgamma. In mice it increased running endurance substantially, produced the transcriptional signature of endurance training in muscle, reduced fat mass in diet-induced obesity and improved cardiac function in heart failure models - all without exercise. It is not a peptide and it is not a receptor everyone is comfortable turning on chronically, since ERRalpha is also upregulated in several cancers.

Targets: ERRalpha (ESRRA), ERRbeta (ESRRB), ERRgamma (ESRRG), PGC-1alpha transcriptional programme, Mitochondrial biogenesis

Dosing

ProtocolDoseFrequencyRoute
Rodent research dosing (for reference only)n/a—twice dailysubcutaneous
Vendor and anecdotal human protocolUsually pre-workout or morning.250 mcg – 500 mcgonce dailysubcutaneous
  • · Published mouse studies used roughly 15-30 mg/kg per day intraperitoneally or subcutaneously. Direct mg/kg scaling to humans is not valid, and this is the reason no honest human dose can be quoted.
  • · These numbers come from vendor marketing, not from any study. They are included because people are using them, not because they are validated. There is no human safety or efficacy data at any dose.

Cycling

Anecdotal use runs 4-8 weeks. Given chronic nuclear receptor activation and the ERRalpha-cancer association, indefinite use is not a sensible plan.

Work out your exact syringe units →

Pharmacology

Half-life
Short in rodents, which is why preclinical work used twice-daily injection. No human pharmacokinetic data exist.
Onset
Rodent endurance changes appeared over roughly 4 weeks of dosing. Nothing is characterised in humans.
Routes
subcutaneous, oral
Molecule
Small-molecule pan-ERR agonist (not a peptide)
Molecular weight
290.32 Da

Handling

Diluent
Bacteriostatic water, though solubility is limited - many vials specify a small amount of DMSO or a co-solvent first
Typical mix
2 or 3 mL
Vial sizes
5, 10 mg
Lyophilised
Fridge or freezer, protected from light.
Reconstituted
Refrigerated; stability in aqueous solution is not well characterised.
Light sensitive
Yes — keep it out of the light

Mixing

This is a small hydrophobic molecule rather than a peptide, so it does not dissolve like one. Cloudy or incompletely dissolved solution means an unreliable dose.

Side effects

  • very commonUnknown human safety profile— Zero human data. Anyone using this is the experiment.
  • commonInjection-site irritation— Co-solvents used to dissolve it are often the cause.
  • uncommonElevated heart rate or palpitations— Reported anecdotally; plausible given ERR effects on cardiac metabolism.
  • rareTheoretical tumour-promotion risk— ERRalpha overexpression is associated with poor prognosis in breast and other cancers; chronic pan-ERR agonism has not been evaluated for this.

Do not use if

  • Active or prior hormone-sensitive cancer - ERRalpha activity is linked to tumour progression in several malignancies.
  • Pregnancy and breastfeeding.
  • Significant cardiac arrhythmia, given the unknown cardiac effects in humans.

Combining it

  • synergyaicar — Both are exercise mimetics acting on overlapping oxidative-metabolism programmes; combining two unvalidated compounds also compounds the unknowns.
  • synergymots-c — Both push mitochondrial function; the pairing is theoretical.

What to monitor

  • · Objective endurance testing - if it works, a time trial or VO2 estimate should move.
  • · Resting heart rate and blood pressure.
  • · Current cancer screening before starting, given the ERRalpha concern.

Legal status

Not approved anywhere; research chemical only. Metabolic modulators of this type fall under WADA's prohibited categories and analytical methods for detecting it have already been published.

References

  • Billon et al. 2023 - synthetic pan-ERR agonist SLU-PP-332 enhances exercise capacity and endurance in mice (preclinical)
  • Preclinical studies of SLU-PP-332 in diet-induced obesity and heart failure models (preclinical)
  • In vitro metabolism and analytical characterisation of SLU-PP-332 and SLU-PP-915 for doping control (other)

Mechanism in depth

The estrogen-related receptors are orphan nuclear receptors - orphan meaning no endogenous ligand has been identified - and they are the transcriptional machinery that skeletal muscle uses to build and maintain its oxidative capacity. ERRalpha partners with PGC-1alpha, and that pairing drives the transcription of essentially the whole mitochondrial and fatty-acid-oxidation programme: the electron transport chain subunits, the beta-oxidation enzymes, the TCA cycle machinery, mitochondrial biogenesis. Genetic work had established that ERRs are important for exercise capacity, but ERRalpha was considered undruggable as an agonist target for years. Billon's contribution was finding SLU-PP-332, a pan-ERR agonist with highest potency at ERRalpha and enough in vivo stability to be a usable chemical tool. What it does is striking: in a skeletal muscle cell line it increased mitochondrial function and cellular respiration, and in mice it increased type IIa oxidative fibres and enhanced running endurance. Critically, Billon showed the compound induces an ERRalpha-specific acute aerobic exercise genetic programme - not a vague metabolic improvement but a recognisable transcriptional signature of an exercise bout - and that ERRalpha activation was necessary for the endurance benefit, demonstrated using ERRalpha-dependent models. That is a stronger mechanistic case than almost anything else in this category. The follow-up work extended it: SLU-PP-332 alleviated metabolic syndrome in diet-induced obese and ob/ob mice with increased energy expenditure, increased fatty acid oxidation and decreased fat mass accumulation, and Xu showed pan-ERR agonism improved heart failure by enhancing cardiac fatty acid metabolism and mitochondrial function. Wang found the same class reversed mitochondrial dysfunction and inflammation in the ageing kidney. So the biology is coherent, reproducible and now supported by multiple independent groups. What does not exist is a single human dose.

What usually goes wrong

The first practical problem is that SLU-PP-332 is probably not an oral drug. The original characterisation described it as having enough stability to be an in vivo chemical tool with twice-daily injection, and the same laboratory subsequently developed SLU-PP-915 specifically as the orally active analogue. If the group that made it needed a new molecule to get oral activity, the capsules being sold are unlikely to be delivering what the mouse studies delivered. The second is that the human dose is invented. The vendor protocols of 250-500 mcg daily bear no derivable relationship to the milligram-per-kilogram dosing used in mice, and nobody has published a scaling. The third is the cardiac question: ERRgamma is highly expressed in heart and Xu showed pan-ERR agonism substantially alters cardiac fatty acid metabolism. In a failing heart that was beneficial. In a healthy heart, chronically, nobody knows. The fourth is that this is detectable - anti-doping laboratories have published metabolite profiles and analytical methods specifically for SLU-PP-332, so anyone in tested sport is taking a straightforward risk.

Bloodwork worth running

MarkerWhenWhy it matters
Liver enzymes - ALT, AST, GGTBaseline, at four weeks, then every twelve weeks.An unstudied small molecule with no human toxicology, taken daily, activating a transcription factor that is highly expressed in liver as well as muscle. This is the minimum monitoring anyone should do.Act if: Any transaminase rise above twice the upper reference limit means stop.
Fasting glucose, insulin and HOMA-IRBaseline and at twelve weeks.The mouse data show improved insulin sensitivity and increased fatty acid oxidation in models of metabolic syndrome. If it translates at all, this is where it appears.Act if: No improvement at twelve weeks means the compound is not doing what it is claimed to do.
Lipid panel with triglyceridesBaseline and at twelve weeks.Increased fatty acid oxidation should move triglycerides. It is a cheap and reasonably direct readout of the proposed mechanism.Act if: Rising triglycerides on a compound sold as a fat-oxidation agent is a reason to stop.
Resting heart rate and, if you have access, VO2max or a validated field testBaseline and at twelve weeks, with the training programme unchanged in between.The claimed effect is endurance capacity. That is measurable without a laboratory - a repeatable field test at baseline and twelve weeks, with training held constant, is worth more than any blood marker for this compound.Act if: No change in performance at twelve weeks with training held constant means it does not work for you.
Creatine kinaseBaseline and at eight weeks.The proposed mechanism includes a fibre-type shift toward type IIa oxidative fibres, which involves genuine remodelling. CK is the cheap way to see whether remodelling is happening or damage is.Act if: Sustained elevation several times the upper reference limit without a training explanation means stop.

Pharmacokinetics

Metabolism
In vitro metabolite profiles have been published by two independent anti-doping groups, so the metabolic fate is partly mapped - but for detection rather than dosing.
Elimination
Not characterised.

Receptor targets

  • Estrogen-related receptor alpha (ERRalpha, NR3B1) — Highest potency of the three subtypes; the specific EC50 was not resolved to a primary source in this session

    The key target. Partners with PGC-1alpha to drive mitochondrial biogenesis, oxidative phosphorylation and fatty acid oxidation gene programmes. Billon showed ERRalpha activation is required for the endurance effect.

  • Estrogen-related receptor beta (ERRbeta, NR3B2) — Agonised, lower potency than ERRalpha

    Contributes to the oxidative fibre-type shift toward type IIa.

  • Estrogen-related receptor gamma (ERRgamma, NR3B3) — Agonised, lower potency than ERRalpha

    Highly expressed in heart; likely mediates much of the cardiac fatty acid oxidation effect reported by Xu.

  • Estrogen receptor alpha and beta — Not an estrogen receptor ligand despite the name

    None. ERRs share sequence homology with estrogen receptors but do not bind estrogens, and SLU-PP-332 is not oestrogenic.

What to expect, and when

No human timeline exists. In mice, the acute exercise transcriptional programme is induced within hours of a dose, while the endurance and body-composition changes required weeks of twice-daily dosing. If you intend to evaluate it in yourself, twelve weeks with a fixed training programme and a repeatable performance test at both ends is the minimum design that could tell you anything.

Stacking and comparisons

The stack that circulates is SLU-PP-332 with AICAR, on the reasoning that AICAR activates AMPK and SLU-PP-332 activates the ERR-PGC-1alpha transcriptional axis, so you are hitting the same oxidative programme from an acute signalling angle and a transcriptional one. That is mechanistically coherent and completely untested. The important thing to understand is that both mimic aspects of endurance training, which means neither substitutes for it - Narkar's AICAR work found the drug plus training was synergistic, not that the drug replaced training. Combining with 5-amino-1MQ has a shared thread through NAD+ and PGC-1alpha, since sirtuin-mediated PGC-1alpha deacetylation requires NAD+ and PGC-1alpha is ERRalpha's partner, but again nobody has tested it. What you should not do is run it alongside anything cardiotoxic or in the presence of known heart disease: Xu's work shows this compound substantially remodels cardiac substrate metabolism, and that is a large intervention in an organ with no margin for error.

Against AICAR, the other exercise mimetic in this class: AICAR has actual human exposure through cardiac surgery trials and therefore some real safety data, but its own endurance evidence rests largely on Narkar's mouse work and it requires impractical doses in humans. SLU-PP-332 has better and more reproducible preclinical biology across several independent groups, and zero human exposure. Against 5-amino-1MQ, the mechanisms are complementary rather than competing - one raises NAD+ availability, the other activates the transcription factor that NAD+-dependent signalling ultimately feeds - and both have the same fundamental problem, which is no human data. Against actual endurance training, nothing here suggests substitution: the compound induced an exercise-like transcriptional programme, and the honest reading is that it may amplify training rather than replace it. Against its own successor, SLU-PP-915 was made because SLU-PP-332 was not orally active, which is the most useful single fact about the version being sold.

Rough cost

$60–$200/month. Sold as capsules or as research-grade powder, typically 50-150 USD a month at vendor-suggested dosing. The price is not the problem; the fact that nobody knows whether oral dosing delivers anything is.

Genuinely uncertain

  • No human data of any kind exist - no pharmacokinetics, no safety, no efficacy, no dose-response.
  • Oral bioavailability is doubtful. The compound was used by injection in the preclinical work and the same laboratory developed a separate molecule to achieve oral activity.
  • The vendor human dose of 250-500 mcg daily has no published derivation and is orders of magnitude below what the mouse work used on a weight-adjusted basis.
  • No authoritative EC50 values for SLU-PP-332 at ERRalpha, beta or gamma were resolved in this session.
  • The long-term consequences of chronic pan-ERR agonism in a healthy human heart are entirely unknown, and ERRgamma is highly expressed in cardiac tissue.
  • Blood-brain barrier penetration is unknown.
  • There is no published analysis of what is in commercially sold SLU-PP-332 products.

Papers