SLU-PP-332
Published research and evidence base
SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRalpha, ERRbeta and ERRgamma), a family of orphan nuclear receptors that act with PGC-1 coactivators to regulate mitochondrial biogenesis and oxidative metabolism. Reported work characterises it as an 'exercise mimetic' because it reproduces part of the acute aerobic exercise transcriptional programme in rodent skeletal muscle, with additional published effects in mouse models of diet-induced obesity, pressure-overload heart failure and kidney ageing. The evidence base is preclinical only: it consists of rodent in vivo studies, cell-based work, medicinal-chemistry optimisation and analytical/doping-control metabolite characterisation. No human clinical trial of SLU-PP-332 has been published or registered, and no human pharmacokinetic or safety data exist.
- Studies cited
- 13
- Published 2023+
- 13
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- Pan-ERR (ERRalpha/beta/gamma) agonism and PGC-1alpha coactivation
- Exercise-mimetic transcriptional response in skeletal muscle
- Mitochondrial biogenesis and fatty acid oxidation
- Metabolic syndrome, diet-induced obesity and insulin sensitivity in rodents
- Cardiac fatty acid metabolism and heart failure models
- Renal ageing, inflammation and mitochondrial dysfunction
- Autophagy regulation via TFEB
- Structure-activity relationship and analogue optimisation (SLU-PP-915 and related series)
- Anti-doping detection and in vitro metabolite profiling
- Absence of human clinical data
Compound identifiers
13 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Systematic review2026
Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications
de Souza-Lima J, Astrosa-Martin BD, Galaz-Rodríguez CA, et al. · Revista Médica de Chile · Systematic review of preclinical literature published 2020-2024 on pan-ERR agonists including SLU-PP-332
The review concluded that pan-ERR agonists reproduced exercise-associated gene expression, increased fatty acid oxidation and improved metabolic parameters across the preclinical studies surveyed, with no evident toxicity reported in those models. All included evidence was preclinical.
- 02Animal in vivo2026
An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity
Billon C, Appourchaux K, Côté I, Burris TP · Journal of Pharmacology and Experimental Therapeutics · Mice; RELATED ERR AGONIST (SLU-PP-915, an orally active analogue) benchmarked against intraperitoneal SLU-PP-332
This study concerns the related ERR agonist SLU-PP-915 rather than SLU-PP-332 itself. Orally dosed SLU-PP-915 improved aerobic exercise performance in mice comparably to injected SLU-PP-332 and induced the acute-exercise marker gene Ddit4, with additive effects alongside training.
- 03Animal in vivo2024
A Synthetic ERR Agonist Alleviates Metabolic Syndrome
Billon C, Schoepke E, Avdagic A, et al. · Journal of Pharmacology and Experimental Therapeutics · Diet-induced obese mice and ob/ob mice treated with SLU-PP-332
Treatment increased energy expenditure and fatty acid oxidation and reduced fat mass in obese mice, with reported improvement in insulin sensitivity. Findings were confined to rodent models of metabolic syndrome.
- 04Animal in vivo2024
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function
Xu W, Billon C, Li H, et al. · Circulation · Mouse pressure-overload (transverse aortic constriction) heart failure model; SLU-PP-332 and the related analogue SLU-PP-915
Both pan-ERR agonists improved ejection fraction, reduced fibrosis and increased survival in mice with pressure-overload heart failure, in association with enhanced cardiac fatty acid metabolism and mitochondrial function. ERRγ was identified as the principal mediator.
- 05Animal in vivo2023
Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity
Billon C, Sitaula S, Banerjee S, et al. · ACS Chemical Biology · Mice, including ERRα-deficient animals; skeletal muscle transcriptomics and treadmill exercise testing
SLU-PP-332 induced an acute aerobic exercise-like transcriptional signature in mouse skeletal muscle, increased type IIa oxidative fibres and improved treadmill endurance. The exercise-capacity effect was reported to be ERRα-dependent.
- 06Animal in vivo2023
Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney
Wang XX, Myakala K, Libby AE, et al. · The American Journal of Pathology · 21-month-old mice treated with SLU-PP-332 for approximately 8 weeks
SLU-PP-332 reduced age-associated albuminuria, podocyte loss and renal inflammatory signalling in aged mice, with changes in STING and STAT3 pathways and improved mitochondrial markers. The effects were described as partially overlapping those of caloric restriction in the same model.
- 07In vitro2026
Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling
Okda HE, Zhao P, Hayes M, et al. · International Journal of Biological Macromolecules · Medicinal chemistry structure-activity relationship series; cell-based ERRα and ERRγ transactivation assays
Systematic analogue synthesis identified structural determinants controlling ERRα versus ERRγ agonism around the SLU-PP-332 scaffold. Several analogues matched the parent compound's potency with reported improvements in drug-like properties.
- 08In vitro2026
In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential
Möller T, Krug O, Thevis M · Rapid Communications in Mass Spectrometry · Human liver preparations (in vitro metabolism); LC-MS/MS and high-resolution mass spectrometry characterisation
Nine metabolites of SLU-PP-332 (six Phase I, three Phase II) and seven Phase I metabolites of the related agonist SLU-PP-915 were identified in vitro. The work was performed to support anti-doping detection methods, not to assess efficacy or safety.
- 09In vitro2026
Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes
Avliyakulov NK, Sobolevsky T, Ahrens E · Drug Testing and Analysis · Human liver S9 fraction incubations with SLU-PP-332; mass spectrometric metabolite profiling
Twenty-two in vitro metabolites of SLU-PP-332 were characterised, of which eight were proposed as the most suitable analytical targets for doping-control screening. The study addressed detectability only.
- 10In vitro2025
Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study
Bonanni R, Falvino A, Matticari A, et al. · Frontiers in Physiology · Primary myoblasts isolated from physically inactive women, treated ex vivo with SLU-PP-332 (pilot study)
In human-derived primary myoblasts, SLU-PP-332 downregulated NOX4 and upregulated SIRT1, PGC-1α, ERRα and FNDC5, with reduced markers of oxidative stress and senescence and increased myotube formation. This was a cell-culture pilot study, not a clinical trial, and no participants were dosed with the compound.
- 11In vitro2024
The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB
Losby M, Hayes M, Valfort A, et al. · Molecular Pharmacology · Neonatal rat ventricular myocytes and C2C12 myoblasts treated with ERR agonists including SLU-PP-332
ERR activation increased TFEB expression and downstream autophagy-related gene transcription in cardiac and muscle cell models. The work defined a transcriptional link between ERR agonism and autophagy rather than testing a whole-animal outcome.
- 12Review2026
Pharmacology of estrogen-related receptors (ERRs) agonists
Radwan MO, Guin S, Burris TP · RSC Chemical Biology · Narrative pharmacology review covering ERR agonist chemotypes, including the SLU-PP series
The review catalogued reported ERR agonist scaffolds and their structure-activity relationships, situating SLU-PP-332 within the broader chemotype landscape. It was written to guide design of next-generation ERR agonists rather than to report new experimental data.
- 13Review2026
Nuclear Receptor-Targeted Therapies: Reprogramming Metabolism with TRβ, ERRα, and LXR Modulators
Di Giovanni C, Lavecchia A · Biomolecules · Review of nuclear-receptor metabolic modulators; RELATED ERR AGONIST pharmacology (JND003, SLU-PP-915) rather than SLU-PP-332 specifically
The review summarised preclinical evidence that ERRα agonists improve insulin resistance and promote lipid oxidation in rodent obesity models, alongside TRβ and LXR modulators. It reported no human efficacy data for the ERRα agonist class.
What this evidence does not establish.
There are no published or registered human clinical trials of SLU-PP-332; a ClinicalTrials.gov query returned no studies, so human pharmacokinetics, dosing, efficacy and safety are entirely unestablished, and long-term toxicity, carcinogenicity and reproductive effects have not been characterised. All reported metabolic, cardiac, renal and exercise-capacity outcomes derive from rodent models or cell culture, including studies of related analogues such as SLU-PP-915, and cannot be extrapolated to humans.
Common questions about the research.
- What is SLU-PP-332?
SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors ERRα, ERRβ, and ERRγ. It is described in the literature as an exercise mimetic chemical probe and is not a peptide.
- What does the evidence base for this compound actually consist of?
Rodent and cell-based experiments only. Every published in vivo characterisation has been carried out in mice by parenteral administration. There are no human clinical trials, no human pharmacokinetic data, and no established human dose for this molecule — a point worth weighing carefully when reading secondary sources that describe it in human terms.
- How does SLU-PP-332 differ from SLU-PP-915?
SLU-PP-915 is a chemically distinct ERR pan-agonist developed later specifically because SLU-PP-332 lacks oral bioavailability. Both remain preclinical research compounds.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.