Quick Answer
SLU-915 is shorthand for SLU-PP-915, a synthetic small molecule (not a peptide) that activates the oestrogen-related receptors ERRα, ERRβ and ERRγ. Developed at Saint Louis University as a chemically distinct relative of SLU-PP-332, it is orally bioavailable in mice. The evidence is limited to cell and mouse studies, almost all from one research network, and there are no human trials.
SLU-915 is not a separate compound. It is an informal shortening of SLU-PP-915, the name used in the peer-reviewed literature, although its developers occasionally use the short form themselves (Losby et al., 2024). It belongs to the same family as SLU-PP-332, the better known exercise mimetic, and shares its central limitation: everything known about it comes from cells and mice.
What SLU-PP-915 is
SLU-PP-915 was first reported in 2023 by John Walker's medicinal chemistry group at Saint Louis University School of Medicine, working with pharmacologist Thomas Burris, now at the University of Florida (Hampton et al., 2023). Chemically it is a thiophene carboxamide carrying a phenylboronic acid group, (3-(5-((2-fluorophenyl)carbamoyl)thiophen-2-yl)phenyl)boronic acid, with the formula C17H13BFNO3S and a molecular weight of about 341. It is not a peptide: like SLU-PP-332, it is a small molecule designed to sit inside the binding pocket of a nuclear receptor.
The target: oestrogen-related receptors
The oestrogen-related receptors (spelled estrogen-related in most of the literature) are nuclear receptors: transcription factors that switch sets of genes on or off. Despite the name, they do not bind oestrogen, and they are active even without a ligand (Radwan et al., 2026). Their target genes govern mitochondrial biogenesis, oxidative phosphorylation and fatty acid oxidation, and ERRα and ERRγ are highly expressed in heart, skeletal muscle and liver.
Because that gene programme overlaps with the muscle response to endurance training, the Burris group describes ERR agonists as candidate exercise mimetics (Billon et al., 2026). It is a coherent hypothesis, so far tested only in animals.
How it differs from SLU-PP-332
Both compounds came from the same programme but from different chemistry. SLU-PP-332 is an acyl hydrazone, made by modifying an older tool compound, GSK4716, to gain ERRα activity (Billon et al., 2023). SLU-PP-915 came from a structure-based search for a new scaffold, and replacing a phenol with a boronic acid kept the activity while improving stability in liver microsome assays (Hampton et al., 2023).
| Feature | SLU-PP-332 | SLU-PP-915 |
|---|---|---|
| Chemical class | Acyl hydrazone | Thiophene carboxamide with a boronic acid |
| Potency in cell assays (EC50) | 98 nM at ERRα, 230 nM at ERRβ, 430 nM at ERRγ | About 380 to 450 nM at ERRα and ERRγ; ERRβ reported as about 435 nM in one paper and about 1,800 nM in another |
| Oral bioavailability in mice | Lacking | Reported |
| Liver microsome stability | Described by its developers as needing further optimisation | Half-life above 60 minutes (human and mouse) |
| Published animal models | Exercise capacity, obesity, kidney ageing, heart failure | Muscle gene expression, exercise capacity, heart failure, brown fat |
Two cautions apply. The potency figures come from reporter assays in engineered cells, not tissue. And the two papers reporting an ERRβ value for SLU-PP-915 disagree, so the fair summary is sub-micromolar activity at ERRα and ERRγ, with ERRβ unsettled.
SLU-PP-332's wider record includes mouse studies in obesity and metabolic syndrome (Billon et al., 2024) and in the ageing kidney (Wang et al., 2023). Neither used SLU-PP-915, although some summaries of the field group the two compounds together.
What the studies show
Discovery and first mouse data (2023)
The discovery paper confirmed direct binding to ERRγ by NMR, found no activity at the classical oestrogen receptors ERα and ERβ, and showed increased expression of ERR target genes such as PGC-1α and PDK4 in cells (Hampton et al., 2023). In mouse quadriceps muscle, Ddit4, Pdk4 and PGC-1α expression rose within an hour, and treated mice ran further and for longer than controls.
Heart failure model (2024)
The largest study so far, a collaboration led from Baylor College of Medicine, tested both compounds in mice with surgically induced pressure-overload heart failure (Xu et al., 2024). SLU-PP-915 served partly as a check: if two structurally unrelated agonists give the same result, the effect probably comes from ERR activation rather than an off-target quirk. Both improved ejection fraction, reduced fibrosis and improved survival over six weeks without changing cardiac hypertrophy, alongside activation of fatty acid and mitochondrial genes.
In mice lacking ERRγ only in heart muscle cells, SLU-PP-915 no longer protected ejection fraction or reduced fibrosis, pointing to ERRγ as the main mediator in the heart. In skeletal muscle, by contrast, the endurance effect of SLU-PP-332 depended on ERRα (Billon et al., 2023). The authors saw no overt toxicity with SLU-PP-915 over six weeks, an incidental observation rather than a safety assessment.
Oral activity and exercise capacity (2026)
The key oral study appeared in the Journal of Pharmacology and Experimental Therapeutics (Billon et al., 2026). In mice it increased running distance and duration to a similar extent as SLU-PP-332 when both were given intraperitoneally, with comparable efficacy when given orally once systemic exposure was accounted for. Both compounds induced Ddit4, a gene switched on by acute aerobic exercise, to levels matching or exceeding treadmill running, depending on the muscle. Combined with exercise training, SLU-PP-915 further increased Ddit4 and mitochondrial gene expression. The authors frame it as a chemical tool for studying long-term ERR activation, which is the most accurate way to see it.
Use as a laboratory probe
SLU-PP-915 now also appears as a probe in mechanism studies. In rat heart muscle cells and mouse C2C12 myoblasts it increased expression of TFEB, a master regulator of autophagy (Losby et al., 2024). In a University of Copenhagen study, with the Burris group as co-authors, short-term treatment raised expression of the thermogenic gene Gpr3 in mouse brown fat, in groups of three animals (Sveidahl Johansen et al., 2026).
What is not known
- Human data. ClinicalTrials.gov lists no trials of SLU-PP-915 or SLU-PP-332 as of October 2026, and no human pharmacokinetic, tolerability or effect data have been published.
- Formal toxicology. Safety observations are incidental notes from mouse studies lasting weeks.
- Binding detail. SLU-PP-915 has not been co-crystallised with an ERR; its binding pose comes from docking models (Radwan et al., 2026).
- A flagged liability. A 2026 review from the Burris group names the electrophilic boronic acid as a drawback, because it can bond covalently to unintended proteins, and suggests replacements (Radwan et al., 2026).
- Human metabolism. The only data are in vitro: anti-doping chemists at the German Sport University Cologne identified seven metabolites using human liver fractions, in the first published metabolism study of the compound (Möller et al., 2026).
- Long-term effects. What sustained activation of all three receptors does across tissues over months has not been studied.
Who is studying it, and why that matters
Almost every primary study involves one network: Walker at Saint Louis University, Burris and Cyrielle Billon, and collaborators at Baylor College of Medicine and the Salk Institute. That is normal for a compound described only three years ago, but independent replication is missing.
The disclosures matter too. The 2026 exercise paper states that SLU-PP-915 is covered by Saint Louis University intellectual property with Burris as an inventor, and that he holds stock in Myonid Therapeutics and Pelagos Pharmaceuticals, both active in developing ERR agonists (Billon et al., 2026). One of the heart failure paper's corresponding authors is a co-founder of and consultant to Pelagos (Xu et al., 2024). This does not invalidate the findings, but the people generating the data have a stake in the class. The only fully independent work so far is analytical: the Cologne group studied SLU-PP-915 because they regard it as having doping potential (Möller et al., 2026).
The bottom line
SLU-PP-915 is credible early-stage pharmacology: a potent, selective, comparatively stable ERR agonist that is orally active in mice, with consistent results across exercise, heart failure and mechanism studies. It is also a preclinical tool compound with cell and rodent data from one research network, no human studies, and a structural feature its own developers would like to engineer out. Descriptions of SLU-915 as a ready-made exercise pill run well ahead of that evidence.
Peptx does not currently stock SLU-PP-915. More coverage of emerging compounds is in the research library.
References
- Hampton CS, et al. (2023). "Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915." European Journal of Medicinal Chemistry258:115582. doi:10.1016/j.ejmech.2023.115582. PubMed 37421886
- Radwan MO, et al. (2026). "Pharmacology of estrogen-related receptors (ERRs) agonists." RSC Chemical Biology 7(7):1265-1277. doi:10.1039/d6cb00077k. PubMed 42256350
- Billon C, et al. (2026). "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. PubMed 41421047
- Billon C, 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. doi:10.1021/acschembio.2c00720. PubMed 36988910
- Billon C, et al. (2024). "A Synthetic ERR Agonist Alleviates Metabolic Syndrome." Journal of Pharmacology and Experimental Therapeutics 388(2):232-240. doi:10.1124/jpet.123.001733. PubMed 37739806
- Wang XX, et al. (2023). "Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney." American Journal of Pathology 193(12):1969-1987. doi:10.1016/j.ajpath.2023.07.008. PubMed 37717940
- Xu W, et al. (2024). "Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function." Circulation 149(3):227-250. doi:10.1161/CIRCULATIONAHA.123.066542. PubMed 37961903
- Losby M, et al. (2024). "The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB." Molecular Pharmacology 106(4):164-172. doi:10.1124/molpharm.124.000889. PubMed 39168657
- Sveidahl Johansen O, et al. (2026). "Cold exposure induces the constitutively active thermogenic receptor, GPR3, via ERRα and ERRγ." Molecular Metabolism 103:102277. doi:10.1016/j.molmet.2025.102277. PubMed 41173363
- Möller T, et al. (2026). "In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential." Rapid Communications in Mass Spectrometry40(8):e70039. doi:10.1002/rcm.70039. PubMed 41588687