SLU-PP-915 vs SLU-PP-332: What the ERR-Agonist Literature Says About the Two Compounds
SLU-PP-915 vs SLU-PP-332 compared from the primary ERR-agonist literature: potency, subtype profile, and the real differentiator — oral bioavailability. RUO.
SLU-PP-915 and SLU-PP-332 are both pan-ERR agonists from the Burris lab. SLU-PP-332 is modestly ERRalpha-preferring and lacks oral bioavailability; SLU-PP-915 is a flatter, roughly equipotent pan-ERR agonist engineered to be orally bioavailable. The real difference reported is pharmacokinetics, not subtype selectivity.
SLU-PP-332 and SLU-PP-915 are two synthetic pan-ERR agonists that emerged from the same laboratory within a few years of each other, and the primary literature now includes a direct head-to-head comparison. The interesting part is that the two compounds are not distinguished by subtype selectivity, the axis most vendor pages emphasise, but by something more mundane and more consequential for any in-vivo work: whether the molecule survives oral administration. Everything below describes laboratory and literature findings — cell assays and mouse studies — not use in people or animals.
What are ERR agonists, and where do these two fit?
Estrogen-related receptors (ERRalpha, ERRbeta, ERRgamma) are orphan nuclear receptors: transcription factors with no confirmed endogenous ligand that nonetheless sit near the centre of oxidative metabolism. They regulate mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and much of the transcriptional program that skeletal muscle activates after endurance exercise.2 That biology is why synthetic ERR agonists are studied as “exercise mimetics” — small molecules that switch on parts of the post-exercise gene response pharmacologically.
SLU-PP-332 was the first well-characterised compound in this line. Reported in ACS Chemical Biology in 2023, it is described as a pan-ERR agonist that “targets all three ERRs but has the highest potency for ERRalpha,” with enough pharmacokinetic exposure to serve as an in-vivo tool in mice.2 SLU-PP-915 came out of a subsequent medicinal-chemistry effort published the same year in the European Journal of Medicinal Chemistry, built on a 2,5-disubstituted thiophene scaffold derived from GSK-4716 rather than the naphthalene benzohydrazide of 332.3 They are chemically distinct series that converge on the same target class.
How do the two compounds compare, structurally and by potency?
The molecules share almost nothing at the level of chemistry. SLU-PP-332 (CAS 303760-60-3, C18H14N2O2, MW 290.32) is an acyl-hydrazide. SLU-PP-915 (CAS 2285432-92-8, C17H13BFNO3S, MW 341.16) is a fluorinated thiophene carrying a boronic acid group — an unusual pharmacophore chosen in part for improved microsomal metabolic stability.3
| Property | SLU-PP-332 | SLU-PP-915 |
|---|---|---|
| Chemical class | Acyl-hydrazide (naphthalene benzohydrazide) | 2,5-disubstituted thiophene, boronic acid |
| CAS | 303760-60-3 | 2285432-92-8 |
| Formula / MW | C18H14N2O2 / 290.32 | C17H13BFNO3S / 341.16 |
| Reported EC50 ERRalpha/beta/gamma (nM) | ~98 / 230 / 430 | ~414 / 435 / 378 |
| Subtype profile | ERRalpha-preferring | Roughly equipotent (flat pan-ERR) |
| Oral bioavailability | Not orally bioavailable (IP tool) | Engineered for oral activity |
Potency values are as reported on reagent-supplier datasheets and in the primary papers; they are not from a single unified assay and should be read as indicative. All figures describe in-vitro and rodent findings only, under Research Use Only terms.
A common framing online has the direction of selectivity backwards. It is SLU-PP-332, not 915, that shows a subtype preference: its reported EC50 of roughly 98 nM at ERRalpha versus 230 and 430 nM at ERRbeta and ERRgamma makes it the more ERRalpha-leaning compound, and the discovery paper says so explicitly.211 SLU-PP-915, by contrast, is described as having “roughly equivalent agonist activity on ERR isoforms alpha and beta,” with reported EC50 values clustered near 400 nM across all three subtypes.312 In absolute terms 915 is the weaker agonist. So if selectivity were the whole story, 332 would look like the more refined tool. It isn’t the whole story.
~400 nM SLU-PP-915’s reported EC50 is roughly equal across all three ERR subtypes — a flat pan-ERR profile, not a selective one.
The real differentiator: oral bioavailability
The point of SLU-PP-915 is pharmacokinetic. SLU-PP-332 improves aerobic performance in mice but is not orally bioavailable, so in-vivo work relies on intraperitoneal injection.1 That is a hard ceiling for any candidate meant to be studied as an orally dosed agent. The 2023 medicinal-chemistry campaign that produced 915 was aimed squarely at that liability, and the boronic-acid moiety it introduced is associated with better microsomal stability.3
The head-to-head appears in a 2026 Journal of Pharmacology and Experimental Therapeutics paper (epub December 2025) that characterises SLU-PP-915 directly against SLU-PP-332.1 It reports that oral SLU-PP-915 matches SLU-PP-332’s exercise-mimetic efficacy — running distance and duration in mice — when the comparison is adjusted for systemic exposure. Both compounds robustly induce Ddit4, a stress-response gene tied to the exercise program, and SLU-PP-915 is reported to synergise with training to further raise Ddit4 and mitochondrial gene expression. In other words, 915 buys a viable oral route without giving up the functional readout, which is the trade the medicinal chemistry was designed to make.
The two compounds are separated not by which receptor subtype they prefer, but by whether the molecule works when it is swallowed.
Context on the phenotype comes from the 332 metabolic-syndrome work: in diet-induced-obese and ob/ob mice, SLU-PP-332 increased energy expenditure and fatty-acid oxidation, decreased fat mass, and improved insulin sensitivity.5 The pan-ERR mechanism also appears to generalise beyond skeletal muscle — a related Circulation study applied the series to a heart-failure model and reported improved cardiac fatty-acid metabolism and mitochondrial function.7 Ongoing SAR work on the 332 scaffold has since mapped which structural features tune ERRalpha versus ERRgamma agonism, efficacy and drug-like properties.6 For a broader look at where this target class sits, see our overview of exercise mimetics, and the individual profiles for SLU-PP-332 and SLU-PP-915. SLU-PP-332 is available as a research reagent on our SLU-PP-332 product page.
An honest read of the evidence
The head-to-head comparison is real and reasonably well documented, but the evidence base has structural weaknesses that are worth stating plainly. Nearly all of the efficacy, selectivity and pharmacokinetic data originate from a single research group (Burris and colleagues), and that group has a direct financial conflict of interest: Burris is a named inventor and holds equity in Myonid Therapeutics and Pelagos Pharmaceuticals, both developing ERR agonists.1 Single-lineage evidence is not automatically wrong, but it has not been independently replicated for the efficacy endpoints, and that matters.
The one genuinely independent thread is anti-doping chemistry. German anti-doping laboratories have characterised the in-vitro human-liver metabolism of both compounds side by side: SLU-PP-332 yielded nine metabolites including three Phase-II conjugates, while SLU-PP-915 yielded only seven Phase-I products, consistent with distinct metabolic fates.48 This is the strongest non-Burris corroboration that the compounds exist and behave as described — but it addresses metabolism and detectability, not whether either compound does anything useful. It also flags both as potential doping agents already on regulators’ radar.
Two further caveats. First, the cross-compound EC50 numbers mix sources: several come from reagent-vendor datasheets rather than one unified assay, so the 332-versus-915 potency comparison combines different assay conditions and should be treated as indicative, not definitive.1112 Second, the exercise-capacity and gene-expression endpoints (Ddit4, mitochondrial genes) are surrogate biomarker readouts. Long-term safety, chronic-dosing effects, and off-target ERR biology — ERRs are also implicated in cancer — are not addressed in these papers. SLU-PP-915’s boronic-acid pharmacophore is chemically unusual and less studied over time than the older 332 scaffold, and there is no human data for either compound at all. General reviews place the target class in context,910 but they do not close these gaps.
All materials supplied by Condor Research are Research Use Only (RUO). Everything summarised here is drawn from in-vitro assays and animal-model literature and is provided for laboratory and literature purposes only. It is not a dosing protocol, clinical guidance, or a safety assessment for any organism, and nothing here concerns human or veterinary use.
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- Both compounds originate in the Burris lab and are pan-ERR agonists acting on ERRalpha, ERRbeta and ERRgamma — orphan nuclear receptors that drive mitochondrial biogenesis and the exercise-adaptation gene program.
- SLU-PP-332 (CAS 303760-60-3) is reported at EC50 ~98/230/430 nM for ERRalpha/beta/gamma, making it the more ERRalpha-preferring of the two.
- SLU-PP-915 (CAS 2285432-92-8) is reported at EC50 ~414/435/378 nM — roughly equipotent across all three subtypes and somewhat less potent in absolute terms.
- The decisive reported difference is pharmacokinetics: SLU-PP-332 is not orally bioavailable (an IP tool in mice), whereas SLU-PP-915 was engineered around a boronic-acid moiety for oral activity.
- In the 2026 JPET paper, oral SLU-PP-915 matched SLU-PP-332's exercise-mimetic efficacy in mice once adjusted for systemic exposure.
- Nearly all efficacy, selectivity and PK data come from a single group with a financial conflict of interest; the only truly independent work is anti-doping metabolism characterization.
- There is no human clinical data for either compound; all findings are cell-based assays and mouse studies.
Which compound is more potent?
By reported EC50 values, SLU-PP-332 is the more potent of the two in absolute terms, particularly at ERRalpha (~98 nM). SLU-PP-915's potency clusters near 400 nM across all three subtypes. Potency alone did not drive the development of 915; oral bioavailability did.
Is SLU-PP-915 more ERRalpha-selective than SLU-PP-332?
No — that framing is reversed. SLU-PP-332 is the ERRalpha-preferring compound; its discovery paper states it has the highest potency for ERRalpha. SLU-PP-915 is described as roughly equipotent across the ERR subtypes, a flatter pan-ERR profile.
Why does oral bioavailability matter so much here?
SLU-PP-332 works in animal studies only by injection, which limits how it can be studied as a candidate. SLU-PP-915 was engineered around a boronic-acid moiety with improved microsomal stability to be orally active, and the 2026 JPET paper reports that it matches 332's exercise-mimetic efficacy when dosed orally and adjusted for exposure.
Are these compounds approved medicines?
No. Neither SLU-PP-332 nor SLU-PP-915 is an approved drug or licensed medicine anywhere. Both are early-stage preclinical research chemicals and candidate molecules.
What is the most independent evidence available?
The strongest non-Burris work is anti-doping metabolism characterisation from German laboratories, which mapped the in-vitro human-liver metabolites of both compounds. It confirms the chemistry and metabolic behaviour but says nothing about efficacy, which remains single-lab.
Is there human data for either compound?
No. All efficacy, metabolic and pharmacokinetic findings are from cell lines or mice. Oral bioavailability was demonstrated in rodents, and whether any of it translates to humans is unestablished.