SLU-PP-915 is a synthetic small molecule and a pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ). It was identified at Saint Louis University through deliberate chemical optimisation of an ERR-agonist series [1]. It is not a peptide and not a protein, it is a low-molecular-weight, boron-containing compound.

Why 915 exists when 332 already did

The most common misreading is to treat SLU-PP-915 as simply a "new version" of SLU-PP-332. Chemically they are different substances: 332 is built on an acylhydrazone core, whereas 915 uses a thiophene scaffold carrying a boronic acid moiety (C₁₇H₁₃BFNO₃S, ~341 g/mol, CAS (Chemical Abstracts Service registry number) 2285432-92-8). The J Pharmacol Exp Ther authors describe 915 explicitly as a chemically distinct pan-ERR agonist [2].

The motivation was purely pharmacokinetic. SLU-PP-332 is rapidly degraded by liver microsomes and was dosed by injection in the original studies [4]. Hampton et al. found that the phenolic or aniline group could be swapped for a boronic acid, preserving receptor activity while markedly improving metabolic stability: T½ ≥ 60 min in both human and mouse liver microsomes [1]. That change gave the series its first orally bioavailable member.

Boron in bioactive molecules is uncommon but not novel, the same tactic underpins approved drugs such as bortezomib and tavaborole. The boronic acid acts as a bioisostere of a hydroxyl group that is less readily conjugated.

The target: ERR and the mitochondrial programme

ERRα/β/γ are orphan nuclear receptors: they have no established endogenous ligand, and their activity is governed largely by availability of the coactivator PGC-1α. Together this axis drives transcription of genes for oxidative phosphorylation, fatty-acid β-oxidation, the TCA cycle and mitochondrial biogenesis [6]. Exercise raises PGC-1α, hence the "exercise mimetic" idea: switch on the same transcriptional programme pharmacologically.

Reported potency for SLU-PP-915 in cell-based reporter assays is EC₅₀ ≈ 414, 435 and 378 nM at ERRα, ERRβ and ERRγ respectively [1]. It is a genuine pan-agonist and does not discriminate between the three isoforms. No activity at the classical estrogen receptors (ERα/ERβ) has been described, despite the name, ERRs are not estrogen receptors.

What the research actually shows

The key study on 915 is Billon et al., 2026 [2], carried out in male C57BL/6 mice. The main observations:

  • orally administered SLU-PP-915 increased aerobic exercise capacity, the effect survived removal of the injection route;
  • both 332 and 915 robustly induced the Ddit4 gene in muscle, at levels matching or exceeding treadmill running;
  • combined with exercise training, 915 further enhanced Ddit4 and mitochondrial gene expression rather than merely substituting for the training stimulus.

That last point deserves emphasis: in this model the compound behaved more like an amplifier of training adaptation than a replacement for it, which is a meaningfully different claim from the popular "pill instead of the gym" framing. Broader metabolic context for the series comes from a separate study in which ERR agonism alleviated features of metabolic syndrome in mice [5], and a systematic structure-activity analysis of the chemotype is available in [7].

The trace 915 leaves in doping control

This compound has an unusual feature for a research reagent: its metabolism has already been characterised by anti-doping laboratories, pre-emptively. Möller, Krug and Thevis (2026) incubated 332 and 915 with human liver microsomes and S9 fractions and identified seven Phase-I metabolites of 915, three of which were synthesised to confirm their structures [3].

The main transformations are amide hydrolysis, oxidation of the boronic acid and hydroxylation; no Phase-II products were detected. From these, mass-spectrometric targets for routine screening were proposed. As of that publication SLU-PP-915 is not on the WADA (World Anti-Doping Agency) Prohibited List, but as a non-approved substance with performance-enhancing potential it is a plausible future addition.

What we do not know

This is the most important section of the monograph. The evidence base for SLU-PP-915 is confined to cell systems and rodents:

  • There are no human clinical studies at all. No safety data, no human pharmacokinetics, and no established human dose.
  • Chronic toxicology is unpublished. ERRα is expressed in skeletal muscle and also in heart, kidney and a range of tumours, so the consequences of sustained systemic pan-ERR activation are unknown.
  • Pan-agonism means simultaneous activation of three isoforms with different tissue distributions; the contribution of each to the observed effects has not been dissected.
  • Few independent groups have worked with 915 so far, most available data originate from a single research programme, and independent replication is lacking.

Laboratory handling

Crystalline powder; cell work typically uses a concentrated DMSO stock. Boronic acids are prone to oxidation and can form anhydrides (boroxines) in the presence of moisture, so dry storage in tightly closed containers at low temperature and avoidance of repeated freeze-thaw cycles both matter. Specific conditions should be checked against the certificate of analysis for the batch in hand.

Supplied strictly for laboratory research use (RUO): not a medicine, supplement or food, not intended for human or veterinary consumption, and with no established human dose.

The related compound from the same programme is SLU-PP-332. The catalogue category is ERR agonists.