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Draft entry. Written from the cited papers but not yet reviewed by a person. Check the references before relying on any claim.
ERR agonist· Exercise mimetic· Mitochondrial

SLU-PP-915

also ERR pan-agonist 915

SLU-PP-915 is a pan-ERR agonist from the lab that made SLU-PP-332. It is a chemically distinct thiophene boronic acid [1] and, unlike SLU-PP-332, it is orally bioavailable. In mice it improved aerobic exercise performance as much as SLU-PP-332 did [2] and protected the heart in a heart-failure model [3]. It has never been tested in humans.

The orally active version of the best-known exercise mimetic; still a mouse-only compound, and banned in sport.

2D chemical structure of SLU-PP-915
C17H13BFNO3S341.2 g/molCID 142532359 ↗
Preclinical6 papers · 2023–2026 · 6 journals
  • meta-analysis
  • RCT
  • trial
  • observational
  • preclinical / case
  • review / patent / other
  • retracted
2023 · preclinical · Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915.2024 · preclinical · Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.2026 · preclinical · An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity.2026 · review · [Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications].2026 · preclinical · In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential.2026 · preclinical · Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes.
in its favour
  • + Orally active in mice, unlike SLU-PP-332
  • + Improved running distance and duration in mice
  • + Improved heart function in a mouse heart-failure model
watch for
  • − No human studies of any kind
  • − Newest of the group; the smallest literature
  • − Falls under WADA's exercise-mimetic ban

Overview

SLU-PP-915 came from a structure-based design program that started from known ERRγ agonists. That program produced a series of 2,5-disubstituted thiophenes, and replacing a phenol with a boronic acid kept their potency [1].

Its selling point over SLU-PP-332 is oral activity. SLU-PP-332 lacks oral bioavailability. SLU-PP-915 improved running distance and duration by about as much when injected, and kept comparable efficacy when taken orally once blood levels were accounted for [2]. In a pressure-overload heart failure model it improved ejection fraction, reduced fibrosis and increased survival, alongside SLU-PP-332 [3].

Mechanism

Like SLU-PP-332, it activates the ERRs, which control mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation and the Krebs cycle. It induces Ddit4, a gene switched on by acute aerobic exercise, at levels matching or exceeding treadmill running [2]. In the heart the benefit ran mainly through ERRγ [3].

Direct targetswhat the molecule itself binds or acts on
  • ERRα / ERRβ / ERRγ nuclear receptorsactivates
    potent pan-ERR agonist designed from an ERRγ template [1]
    strong
Downstreamconsequences of that action, not targets of their own
  • Aerobic exercise gene programactivates
    induces the exercise gene Ddit4 at or above treadmill-running levels [2]
    moderate

Safety

risks and cautions, not medical advice

There is no human safety data. The animal literature reports no evident toxicity in obesity models, and clinical trials are still needed [4]. In human liver preparations it formed seven phase I metabolites and no phase II conjugates. Anti-doping laboratories characterised these because of its doping potential [5].

Adverse effects
reported, not universal
  • None established; no human exposure has been studied
Cautions
who should think twice
  • Exercise mimetics are prohibited in sport by WADA [6]
  • Not approved; product identity and purity unverified; the boronic acid group is unusual in supplements
Limits of the evidence
what has not been shown
  • Every efficacy result is from mice [2][3]
  • Its dedicated literature is only a few papers, all from a small number of labs

Interactions

documented pairs only, not exhaustive
  • SLU-PP-332
    caution
    Same receptors, same mechanism; combining them duplicates one lever and has never been studied

FAQ

What is the difference between SLU-PP-332 and SLU-PP-915?
Both activate all three ERRs. SLU-PP-915 is a chemically different thiophene boronic acid [1], and it works orally in mice where SLU-PP-332 does not [2].

References

entry last reviewed 2026-09-18
  1. [1]
    Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915.
    Hampton CS, Sitaula S, Billon C et al.Eur J Med Chem 2023preclinical · cellPMID 37421886◌ unreviewed
  2. [2]
    An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity.
    Billon C, Appourchaux K, Côté I et al.J Pharmacol Exp Ther 2026preclinical · animalPMID 41421047◌ unreviewed
  3. [3]
    Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.
    Xu W, Billon C, Li H et al.Circulation 2024preclinical · animalPMID 37961903◌ unreviewed
  4. [4]
    [Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications].
    de Souza-Lima J, Astrosa-Martin BD, Galaz-Rodríguez CA et al.Rev Med Chil 2026reviewPMID 42024694in Spanish◌ unreviewed
  5. [5]
    In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential.
    Möller T, Krug O, Thevis MRapid Commun Mass Spectrom 2026preclinical · cellPMID 41588687◌ unreviewed
  6. [6]
    Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes.
    Avliyakulov NK, Sobolevsky T, Ahrens EDrug Test Anal 2026preclinical · cellPMID 41688415◌ unreviewed