SLU-PP-332 vs SLU-PP-915
What the Published Data Show

SLU-PP-332 and SLU-PP-915 are small-molecule research compounds—not peptides—designed to activate ERRα, ERRβ, and ERRγ. These nuclear receptors help regulate mitochondrial biogenesis, oxidative metabolism, and transcriptional adaptations associated with aerobic exercise.

SLU-PP-332 is the more ERRα-potent benchmark compound, but published mouse studies use it primarily by intraperitoneal injection because it lacks useful oral bioavailability. SLU-PP-915 was developed on a different chemical scaffold with better metabolic stability and measurable oral activity. When exposure was accounted for, both compounds increased mouse running performance and induced the exercise-responsive gene Ddit4.

The evidence remains preclinical. Neither compound has established human dosing, safety, efficacy, or long-term risk data.

SLU-PP-332 grew out of optimization work around earlier ERR ligands and uses an acyl-hydrazone-derived scaffold. SLU-PP-915 emerged from a separate 2,5-disubstituted thiophene series incorporating a boronic-acid group. The 2023 medicinal-chemistry paper reported improved microsomal stability for the 915 series and identified SLU-PP-915 as an orally active lead.

That structural separation matters scientifically. When unrelated chemotypes produce overlapping phenotypes, the observation is less likely to be explained solely by an idiosyncratic off-target effect from one scaffold. It does not eliminate off-target uncertainty, but it strengthens the case for investigating ERR activation as the shared driver.

Cell-based cotransfection assays place SLU-PP-332 at roughly 98 nM for ERRα, 230 nM for ERRβ, and 430 nM for ERRγ. Reported values for SLU-PP-915 are approximately 414, 435, and 378 nM, respectively. On that assay basis, 332 is more potent at ERRα, while 915 produces a more balanced pan-ERR profile.

These values should not be read as a clinical potency ranking. They come from transcriptional reporter systems, and assay format can affect absolute EC50 values. More importantly, receptor potency alone does not determine systemic exposure, tissue distribution, metabolism, or in-vivo efficacy.

The original SLU-PP-332 studies established adequate exposure after intraperitoneal dosing for use as an in-vivo chemical probe. Subsequent work explicitly described it as lacking oral bioavailability. SLU-PP-915 was optimized to address that limitation.

A later comparative mouse study reported that oral SLU-PP-915 retained exercise-mimetic activity when systemic exposure was matched. Its oral plasma half-life was short, and the study did not show drug-like persistence appropriate for assuming once-daily human use. The result is better understood as proof that the ERR program can be engaged orally in mice—not as a clinical dosing template.

The 2023 SLU-PP-332 study reported increased oxidative muscle-fiber characteristics, mitochondrial markers, and treadmill endurance. Genetic experiments showed that ERRα was required for the endurance response, linking the phenotype to the intended receptor pathway.

Comparative work with SLU-PP-915 found that both compounds increased running time and distance after short dosing protocols. Both also induced Ddit4, a gene that rises after acute aerobic exercise. In some comparisons, 915 produced a larger Ddit4 response or reached similar performance effects at a lower intraperitoneal dose.

Those findings do not make either compound a substitute for exercise. Treadmill performance and transcriptional overlap capture selected endpoints; physical training affects many systems that these experiments did not reproduce or measure.

In a mouse transverse-aortic-constriction model, both agonists improved ejection fraction, reduced fibrosis, and increased survival without preventing the hypertrophic response itself. Multi-omics and genetic-dependency work connected the benefit to improved fatty-acid metabolism, mitochondrial function, and ERR signaling.

Some reported measures favored SLU-PP-915, including aspects of stroke volume, cardiac output, or recovery timing. Those differences came from one preclinical program and should be treated as hypothesis-generating rather than proof of therapeutic superiority.

SLU-PP-332 provided early in-vivo evidence that pan-ERR activation can reproduce part of an aerobic-exercise transcriptional program and improve selected metabolic and cardiac endpoints in mice. SLU-PP-915 showed that a distinct scaffold can reach similar biology while adding oral exposure.

The literature therefore supports a pathway-level conclusion more strongly than a compound-level winner. SLU-PP-915 offers the clearer pharmacokinetic advantage, while SLU-PP-332 has the broader published benchmark record. Neither has crossed the evidence boundary from preclinical probe to established human intervention.

For background on the benchmark molecule, see our SLU-PP-332 research guide. To evaluate the testing documents attached to any research product, use our guide to reading a peptide COA and review how Peptide Protocols COA grades separate identity, purity, quantity, and laboratory transparency.