SLU-PP-332
A small-molecule pan-ERR agonist marketed as 'exercise in a pill' with reproducible endurance and fat-oxidation data in mice and zero human evidence.
SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ) developed in the Thomas Burris laboratory at Saint Louis University as a chemical probe for exercise-mimetic pharmacology. By activating the ERR/PGC-1α axis, it switches on the same oxidative-metabolism gene program that endurance training produces, and in mice it increased running endurance, mitochondrial content, and fatty-acid oxidation. It is not a peptide despite being sold alongside them, it is not orally bioavailable, and it has no registered human clinical trials, pharmacokinetics, or safety data.
Class
Synthetic small-molecule pan-ERR (ERRα/β/γ) agonist (acylhydrazone); not a peptide
Routes
Intraperitoneal injection (rodent studies), Subcutaneous / intramuscular (community self-report only)
Category
Weight Loss & Metabolic
Researched benefits
What it's studied for
Exercise-mimetic gene program
In mouse skeletal muscle SLU-PP-332 induces an ERRα-dependent acute-aerobic-exercise gene signature — the same transcriptional program a bout of endurance running produces — by directly activating ERRs and improving PGC-1α coactivator recruitment. The mimicry is metabolic and oxidative; it does not reproduce strength, cardiovascular conditioning, tendon/bone loading, or the systemic effects of training.
Increased endurance capacity
In the foundational study, sedentary mice given SLU-PP-332 ran roughly 70% longer and about 45% farther than vehicle controls without prior training. This is an animal result at injected doses with no human validation.
Enhanced fat oxidation
In diet-induced-obese mice dosed by injection for four weeks, treatment reduced fat-mass accumulation and raised whole-body energy expenditure and fatty-acid oxidation without reducing food intake, reflecting upregulation of fatty-acid-oxidation enzymes (CPT1, ACADM/ACADL, HADHA/HADHB).
Mitochondrial biogenesis
The compound increased mitochondrial content (measured by electron microscopy and respirometry) and drove expression of mitochondrial-biogenesis factors (NRF1, NRF2, TFAM) via the ERR/PGC-1α axis in rodent muscle.
Muscle fiber-type shift
SLU-PP-332 increased oxidative (type IIa / slow-twitch) fiber markers such as MYH7, producing a muscle phenotype resembling endurance-trained tissue in mice.
Cardioprotection (preclinical)
In pressure-overload cardiac hypertrophy and heart-failure models, SLU-PP-332 preserved or improved cardiac function and reduced pathological remodeling — effects attributed mainly to ERRγ and the heart's dependence on fatty-acid oxidation.
Mechanism
How it works
SLU-PP-332 is a synthetic small-molecule agonist of the three estrogen-related receptors (ERRα/NR3B1, ERRβ/NR3B2, ERRγ/NR3B3), a subfamily of orphan nuclear receptors that lack well-characterized endogenous ligands and are constitutively active. Because these receptors are already 'on,' pharmacologic activation means stabilizing receptor conformations that improve coactivator recruitment and transcriptional output rather than switching a dormant receptor on. SLU-PP-332 binds the ligand-binding domain of all three isoforms and preferentially recruits PGC-1α, the master regulator of mitochondrial biogenesis and oxidative metabolism.
ERRs are the transcription factors through which the exercise-induced coactivator PGC-1α runs its mitochondrial program: oxidative phosphorylation, the TCA cycle, fatty-acid oxidation, and mitochondrial biogenesis. By activating ERRs directly, SLU-PP-332 turns that program on without exercise. The downstream response is a coordinated upregulation of mitochondrial-biogenesis factors (NRF1, NRF2, TFAM), fatty-acid-oxidation enzymes (CPT1A/CPT1B, ACADM/ACADL/ACADVL, HADHA/HADHB), TCA-cycle and electron-transport-chain components, mitochondrial fusion/fission machinery (MFN1, MFN2, OPA1, DRP1), and slow-twitch markers (MYH7), shifting cellular metabolism from glycolysis toward oxidative phosphorylation.
The pan-agonist profile — hitting ERRα, ERRβ, and ERRγ simultaneously — captures the full tissue-distributed metabolic program rather than a restricted subset. ERRα is broadly expressed in metabolically active tissues (skeletal muscle, heart, brown fat, liver, kidney), ERRβ is enriched in undifferentiated and neural cells, and ERRγ is enriched in heart, slow-twitch muscle, and brown fat. SLU-PP-332 does not activate the classical estrogen receptors. It is most potent at ERRα (cell-based EC50 ~98 nM).
Important limitations frame the mechanism. Driving tissues toward oxidative metabolism reproduces the transcriptional signature of exercise but not its mechanical loading, cardiovascular conditioning, or neuroendocrine effects — it is a transcriptional exercise mimetic, not an exercise replacement. Sustained ERR activation may trigger homeostatic adaptation (receptor downregulation, coactivator redistribution) that attenuates the effect over time, on an unknown human timescale. Critically, SLU-PP-332 has poor oral bioavailability and rapid clearance; every published rodent study used intraperitoneal injection, which is why the same lab engineered the orally bioavailable successor SLU-PP-915.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Beginner (community self-report)
- Dose
- 3-5 mg
- Frequency
- Every other day
- Timing
- Not specified
- Duration
- Typically 6-12 week cycles
- Route
- Subcutaneous or intramuscular injection
Extrapolated from rodent i.p. dosing with no clinical validation. Oral capsules sold by vendors are not supported by the research because the molecule is not orally bioavailable.
Intermediate (community self-report)
- Dose
- 5-10 mg
- Frequency
- Once daily
- Timing
- Not specified
- Duration
- Typically 6-12 week cycles
- Route
- Subcutaneous or intramuscular injection
Daily injection burden is substantial; many users migrate to the oral successor SLU-PP-915 for this reason.
Advanced (community self-report)
- Dose
- 10-20 mg
- Frequency
- Once daily
- Timing
- Not specified
- Duration
- Typically 6-12 week cycles
- Route
- Subcutaneous or intramuscular injection
No human efficacy or safety data supports these upper doses; entirely uncontrolled community practice.
- There are no established human doses. Published rodent studies used approximately 10-50 mg/kg by intraperitoneal injection.
- All human-use dosing figures come from uncontrolled community self-report, not clinical data.
- The compound is not orally bioavailable, so oral capsule products contradict the route (injection) that produced the preclinical results.
- Users seeking an orally active ERR pan-agonist are generally directed to the second-generation successor SLU-PP-915.
Evidence
Research & clinical studies (4)
Discovery and characterization of SLU-PP-332, an ERR agonist that induces an acute-exercise gene program and increases endurance in mice
The foundational Billon et al. study showed SLU-PP-332 induces an ERRα-dependent acute-exercise gene signature in muscle, and sedentary mice ran roughly 70% longer and about 45% farther than vehicle controls.
ERR pan-agonism improves metabolic syndrome parameters in diet-induced obese mice
In diet-induced-obese mice dosed by injection for four weeks, SLU-PP-332 reduced fat-mass accumulation, raised energy expenditure and fatty-acid oxidation, and improved glucose tolerance without reducing food intake.
ERR agonism protects against pathological cardiac remodeling and heart failure
In pressure-overload heart-failure models, SLU-PP-332 preserved or improved cardiac function and reduced pathological remodeling, with effects mediated mainly by ERRγ.
ERR activation and the aging kidney
Follow-on work extended SLU-PP-332's ERR-agonist metabolic effects to protection against features of kidney aging in rodent models.
Combinations
Stacking & blends
Metabolic / mitochondrial support
Amplify oxidative metabolism and fatty-acid utilization
Sources flag MOTS-c and L-Carnitine as synergistic with SLU-PP-332, pairing ERR/PGC-1α-driven mitochondrial biogenesis with substrate delivery and mitochondrial signaling. Entirely theoretical; no human combination data.
Oxygen-delivery / endurance
Explore endurance and metabolic-uncoupling combinations
BAM15 (mitochondrial uncoupler) and ITPP (hemoglobin oxygen-release effector) are listed as compatible with SLU-PP-332 in interaction data. Combination is speculative and unstudied in humans.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Active or recent cardiovascular disease (recent MI within 6 months, unstable angina, decompensated heart failure, uncontrolled hypertension, significant arrhythmias)
- Hormone-sensitive cancer history or current disease (ERRs share homology with estrogen receptors; ERRα linked to unfavorable breast cancer phenotypes preclinically)
- Pregnancy and breastfeeding (absolute)
- Children and adolescents
- Uncontrolled thyroid disease or diabetes (relative)
- Significant hepatic or renal impairment
- Autoimmune disease on immunomodulatory therapy (relative)
- Known hypersensitivity to the compound or preparation components
Short mouse studies reported no overt toxicity (normal blood counts and electrolytes, no rise in a muscle-damage marker), but there is no human safety data and no long-term, reproductive, or carcinogenicity testing. Broad ERR activation across heart, liver, and kidney is an unresolved theoretical safety question. Drug-drug interactions are uncharacterized; theoretical concerns include other nuclear-receptor agonists, CYP450 substrates, cardiac and diabetes medications, anticoagulants, and statins. The most important limitation is the absence of clinical oversight for an unvalidated nuclear-receptor agonist.
FAQ
SLU-PP-332 — common questions
Is SLU-PP-332 a peptide?
No. It is a small-molecule acylhydrazone with no amino-acid backbone. It is frequently mislabeled a 'peptide' because it is sold through the same research-chemical channels as peptides.
Is SLU-PP-332 an 'exercise in a pill'?
Only in a narrow, mechanistic sense, and not in humans. In mice it activates the same ERR/PGC-1α oxidative-metabolism gene program that endurance training switches on and increased running endurance. It does not reproduce the strength, cardiovascular-conditioning, or systemic effects of real exercise, and no human study has tested any of it.
Has SLU-PP-332 been tested in humans?
No. As of 2026 there are no published Phase 1 or later trials, no publicly disclosed IND applications, and no registered trials on ClinicalTrials.gov. The evidence base is entirely preclinical — cell assays and rodent pharmacology, primarily from the Burris laboratory.
Can you take SLU-PP-332 orally?
Not effectively. It has poor oral bioavailability established in the original rodent studies, all of which used intraperitoneal injection. Oral dosing is not expected to produce meaningful systemic exposure. Users wanting an oral ERR pan-agonist are directed to the second-generation compound SLU-PP-915.
What is the difference between SLU-PP-332 and SLU-PP-915?
Both are pan-agonists of the same ERR receptors with similar biological effects in rodents. The key difference is oral bioavailability: SLU-PP-332 has poor oral PK and required injection, while SLU-PP-915 was engineered by the same lab as an orally bioavailable successor. Most users preferring oral dosing have migrated to SLU-PP-915.
Does SLU-PP-332 work for fat loss?
In diet-induced-obese mice it reduced fat-mass accumulation and raised fatty-acid oxidation without reducing food intake — but those are animal results at injected doses. There is no human fat-loss data, and the compound is not orally bioavailable, so consumer-style oral use is not supported by the research.
Is SLU-PP-332 safe?
Unknown in humans. Short mouse studies reported no overt toxicity, but there is no human safety data and no long-term, reproductive, or carcinogenicity testing. Broad activation of ERRs across the heart, liver, and kidney is a theoretical safety question that has not been resolved.
Is SLU-PP-332 FDA approved?
No. It has no approval for any use and is not in any registered human trial. It is sold under research-chemical labeling and is a prohibited substance class in sport (metabolic modulators / exercise mimetics), with published anti-doping detection methods.
