What Is SLU-PP-915? The Orally Bioavailable ERR Agonist the Literature Is Now Characterizing
SLU-PP-915 is a synthetic, orally bioavailable pan-ERR agonist. What the mouse and in-vitro literature actually shows, and where the evidence is still thin.
SLU-PP-915 is a synthetic pan-ERR agonist that activates the estrogen-related receptors ERRα, ERRβ and ERRγ. A boronic-acid thiophene, it is the orally bioavailable successor to SLU-PP-332. In mice, oral dosing reproduced an exercise-related gene program. It is a research chemical with no approved use.
SLU-PP-915 is a small synthetic molecule that turns on a family of orphan nuclear receptors called the estrogen-related receptors (ERRs). It belongs to a short chemical lineage out of Saint Louis University built around one goal: an ERR agonist you can dose by mouth. In December 2025 the first paper dedicated to characterizing its oral activity in mice appeared, which is why the compound is now surfacing in search results and supplier catalogs. Everything below describes laboratory and animal literature findings, not use in people.
What is SLU-PP-915, structurally?
SLU-PP-915 is a 2,5-disubstituted thiophene bearing a boronic acid group. Its CAS number is 2285432-92-8, its molecular formula is C17H13BFNO3S, and its molecular weight is 341.16.7 The IUPAC name is (3-(5-((2-fluorophenyl)carbamoyl)thiophen-2-yl)phenyl)boronic acid.8 In the medicinal-chemistry paper that introduced it, the molecule is compound “10s” — one entry in a synthesized series screened for ERR agonism.2
The boronic acid is the point of the design, not decoration. The parent compound in this lineage, SLU-PP-332, activates the ERRs but is not orally bioavailable, which limits how it can be studied in vivo. The Hampton and Walker series set out to fix that, and the boronic-acid moiety on 915 was selected because it improved microsomal metabolic stability relative to earlier analogs.2 That is the whole reason SLU-PP-915 exists as a named compound: it is the parent’s chemistry re-engineered so the molecule survives long enough after oral dosing to do something measurable.
What does it actually do at the receptor?
The estrogen-related receptors are orphan nuclear receptors — transcription factors with no known natural ligand — that sit upstream of a large chunk of the cell’s energy machinery. When active, they drive mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation and the tricarboxylic-acid cycle. SLU-PP-915 is a pan-ERR agonist, meaning it activates all three isoforms rather than one. Reported in-vitro potency is balanced across them, with EC50 values near 414, 435 and 378 nM for ERRα, ERRβ and ERRγ respectively.8
The ERRα coverage is the historically hard part. The scaffold this whole lineage descends from began as an ERRβ/γ-selective agonist derived from GSK4716, and the chemical-biology work to convert it into a pan-agonist — engineering ERRα agonism into a molecule that did not have it — is what made these tools valuable in the first place.6 A pan-ERR agonist that includes ERRα is not just a slightly broader version of an ERRγ ligand; it reaches a receptor that had resisted drugging.
3 isoforms — ERRα, ERRβ and ERRγ — are activated together by a pan-ERR agonist, which is exactly why systemic effects are hard to predict.
Why is it called an “exercise mimetic”?
The label comes from the parent compound. In 2023, SLU-PP-332 was shown to trigger an ERRα-dependent acute-aerobic-exercise gene program in skeletal muscle and to improve exercise capacity in mice.3 In other words, activating the ERRs reproduced part of the transcriptional signature that a bout of endurance exercise produces — hence “exercise mimetic.” A signature induced gene in this program is Ddit4 (also called REDD1); the receptors also push PGC-1α, PDK4 and LDHA.2
SLU-PP-915 was designed to carry that same activity into an oral molecule, and the December 2025 JPET paper is where that was tested directly. In mice, oral SLU-PP-915 enhanced aerobic exercise capacity — measured as distance and duration — comparably to intraperitoneal SLU-PP-332 once the comparison was adjusted for systemic exposure. It robustly induced Ddit4, and when combined with exercise training it further raised mitochondrial gene expression.1 That paper is the specific reason the compound is now being characterized as an orally active ERR agonist rather than a bench curiosity.
The oral-activity result in mice is real and recent — but “in mice” is doing a lot of work in that sentence.
What has been shown with the class
Beyond exercise capacity, the broader ERR-agonist literature spans several organ systems. It is worth being precise about which compound was used in each, because most of it was the parent, not 915.
| Finding (animal / in-vitro only) | Compound tested | Reference |
|---|---|---|
| Enhanced aerobic exercise capacity, oral dosing | SLU-PP-915 | PMID 41421047 |
| Acute-exercise gene program, improved exercise capacity | SLU-PP-332 | PMID 36988910 |
| Reduced adiposity, improved metabolic parameters (metabolic syndrome model) | SLU-PP-332 | PMID 37739806 |
| Improved cardiac function, reduced fibrosis, better survival (heart-failure model) | SLU-PP-332 and SLU-PP-915 | PMID 37961903 |
| Reversed markers of kidney aging | SLU-PP-332 | PMID 37717940 |
| Induced autophagy via TFEB in cardiomyocytes (mechanism) | ERR agonists (class) | PMID 39168657 |
Every row is a cell-culture or mouse finding. None of it involves human subjects, and none of it is a use recommendation. The heart-failure study is the one place SLU-PP-915 itself was tested in vivo alongside the parent.4
The heart-failure work found that both SLU-PP-332 and SLU-PP-915 improved ejection fraction, reduced fibrosis and increased survival in a pressure-overload mouse model, apparently by boosting cardiac fatty-acid metabolism and mitochondrial function, with genetic studies confirming ERR-isoform dependency.4 On the metabolic side, SLU-PP-332 reduced adiposity and improved metabolic parameters in a mouse metabolic-syndrome model,11 and an eight-week course in aged mice reversed age-related albuminuria, podocyte loss, mitochondrial dysfunction and inflammation in the kidney via cGAS-STING and STAT3 signaling.5 Mechanistically, ERR agonists have also been shown to induce autophagy in cardiomyocytes by making TFEB a direct ERR target gene.9
An honest read of the evidence
This is where the caveats matter more than the headlines. Almost every in-vivo efficacy result for SLU-PP-915 and SLU-PP-332 comes from a single lab lineage — the Burris and Walker groups and their close collaborators. Independent replication of the exercise and metabolic phenotypes by unrelated labs does not yet exist. The one clearly independent characterization of SLU-PP-915 to date is analytical: an anti-doping group profiled both compounds by LC-HRMS/MS and human liver S9/microsome metabolism, identifying seven Phase-I metabolites for 915 (three confirmed by synthesis and NMR) and flagging the class as relevant to sports-drug testing.6 That is genuinely independent work, but it is metabolism chemistry, not efficacy — nobody outside the originating lineage has yet reproduced the exercise or metabolic benefits.
There is also no human data at all. Every efficacy claim is in mice or in cultured cells such as C2C12 myoblasts and cardiomyocytes. There are no clinical trials, no human pharmacokinetics, and no human safety data. “Orally bioavailable” has been demonstrated in rodents, not people. The preclinical studies also tend to use modest mouse cohorts over weeks-long dosing windows, so long-term consequences of chronic pan-ERR activation are simply uncharacterized. And because pan-agonism hits ERRα, ERRβ and ERRγ together, and these receptors are broadly expressed, systemic activation carries theoretical concerns — including proliferation-linked pathways — that short preclinical studies are not powered to detect.
One more distinction is easy to blur: the compound-specific evidence for 915 is still thin. The dedicated oral paper is very recent and focused on exercise-capacity and gene-expression endpoints; much of the metabolic-syndrome, kidney and mechanistic literature was done with SLU-PP-332. Reading those parent-compound benefits directly onto 915 is inference, not established fact. Some of the widely repeated numbers — the EC50 potencies, the CAS and formula — trace to vendor datasheets and secondary reviews and should be attributed to the primary discovery paper rather than treated as independently confirmed.2 A 2026 systematic review of ERR agonists as exercise mimetics is a useful map of the field, but it is a review, not new primary data.10 For readers comparing agents in this space, our notes on the parent compound SLU-PP-332, on exercise mimetics as a category, and on AICAR and AMPK lay out the same evidence standards.
All materials supplied by Condor Research are Research Use Only (RUO). The findings above describe in-vitro assays and animal studies from the published literature only. Nothing here is a dosing protocol, clinical guidance, or a safety assessment for any organism, and none of it should be read as a claim of benefit in humans or animals. SLU-PP-915 available through Condor Research (catalog listing) is a laboratory reference chemical for in-vitro and analytical work.
Condor Research · Scientific desk
Atrio Sciences s.r.o., IČO 57 669 651, Nitra (SK) · info@condorresearch.com
- SLU-PP-915 is a synthetic pan-ERR agonist (ERRα/β/γ) from the Burris/Walker lab at Saint Louis University, engineered as the orally bioavailable successor to the parent compound SLU-PP-332, which lacks oral bioavailability.
- Its chemistry is distinctive: CAS 2285432-92-8, formula C17H13BFNO3S, MW 341.16 — a 2,5-disubstituted thiophene carrying a boronic acid group that was chosen to improve microsomal metabolic stability. In the discovery paper it is compound '10s'.
- Reported in-vitro potency is balanced across isoforms, with EC50 values near 414, 435 and 378 nM for ERRα, ERRβ and ERRγ — including agonism at the historically hard-to-drug ERRα.
- The December 2025 JPET paper (PMID 41421047) reported that oral SLU-PP-915 enhanced aerobic exercise capacity in mice comparably to intraperitoneal SLU-PP-332 after adjusting for systemic exposure, and robustly induced the stress-response gene Ddit4.
- Most of the broader metabolic, cardiac and kidney-aging findings attributed to 'the class' were actually demonstrated with the parent SLU-PP-332, not with SLU-PP-915 — so extending those benefits to 915 is inference, not proof.
- Essentially all in-vivo efficacy data originate from a single lab lineage; the only clearly independent characterization of 915 to date is analytical/metabolism chemistry from an anti-doping group, not efficacy replication.
- There is no human data of any kind. Every efficacy finding is in mice or cell culture, and SLU-PP-915 has been flagged as a potential future doping agent. It is Research Use Only.
What is SLU-PP-915 in one sentence?
It is a synthetic, orally bioavailable pan-ERR agonist — a small molecule that activates the estrogen-related receptors ERRα, ERRβ and ERRγ — developed as the successor to SLU-PP-332. It is characterized only in cell and animal studies and has no approved use.
How is it different from SLU-PP-332?
SLU-PP-332 is the parent scaffold and is not orally bioavailable. SLU-PP-915 is a chemically distinct boronic-acid thiophene engineered for better microsomal metabolic stability, which is what allows it to work when dosed by mouth in mice.
What did the December 2025 paper actually show?
In mice, oral SLU-PP-915 enhanced aerobic exercise capacity comparably to intraperitoneal SLU-PP-332 after adjusting for systemic exposure, robustly induced the gene Ddit4, and combined with exercise training to further raise mitochondrial gene expression. These are animal and gene-expression endpoints, not human outcomes.
Are the metabolic, heart and kidney benefits proven for 915?
Mostly no. The heart-failure study tested 915 directly alongside the parent, but the metabolic-syndrome and kidney-aging findings were generated with SLU-PP-332. Extending those to 915 is a reasonable hypothesis, not a demonstrated result.
Has anyone outside the original lab confirmed the findings?
Not for efficacy. The only clearly independent work so far is an anti-doping lab's analytical and metabolism characterization of both compounds, which identified metabolites and flagged the class for sports-drug testing. The exercise and metabolic phenotypes have not yet been independently replicated.
Why is it associated with doping?
Because ERR agonists mimic parts of the exercise gene program, anti-doping researchers have characterized SLU-PP-915 and SLU-PP-332 as compounds of potential interest for future sports-drug surveillance and have already worked out how to detect their metabolites. That is a research and detection concern, not an endorsement of any use.