SLU-PP-915
SLU-PP-915 — the orally-active "exercise mimetic": fixing SLU-PP-332, the doping tests, and the conflicts

Class: small_molecule
Synonyms: SLU-PP-915
"915"
orally-active pan-ERR agonist (ERRα/β/γ)
Function tags: metabolic
endurance / aerobic capacity (exercise mimetic)
mitochondrial biogenesis / fat oxidation
(oral — the differentiator)
Overall evidence grade: B
WADA prohibited: yes
WADA note: Sport as an exercise mimetic in the ERR class (alongside SLU-PP-332), it is squarely in anti-doping crosshairs — with detection methods actively under development (see Intrigue #3). Realistically WADA-relevant / prohibited-category territory for the class.
Last updated: 2026-07-13

In brief: SLU-PP-915 is a small-molecule pan-ERR agonist — an "exercise mimetic" — and the orally-active successor to SLU-PP-332 (#60) from the same lab (Thomas Burris). By activating the estrogen-related receptors (ERRα/β/γ), it switches on genes for mitochondrial biogenesis, fat oxidation, and the Krebs cycle, mimicking the muscle's response to aerobic exercise and boosting endurance in mice. Its whole reason for existing is intrigue #1: its predecessor #60 couldn't be absorbed orally, so the lab engineered 915 — a chemically different molecule (boronic-acid thiophene) that works by mouth at a lower dose, the first ERR agonist to do so. The intrigue deepens: anti-doping labs are already building tests to catch it (as they did for AICAR #64), and its inventor holds equity in companies developing ERR agonists — a declared conflict worth noting. The decisive caveat is unchanged from #60: it's a small molecule (not a peptide), it has zero human data, and it's unapproved. So: a cleverly engineered "exercise pill" that fixed the delivery problem in mice — genuinely interesting chemistry, still entirely preclinical, and already a doping-control target.

## Identity a **synthetic small molecule** that activates the **estrogen-related receptors (ERRα, ERRβ, ERRγ)** — orphan nuclear receptors — to mimic aspects of aerobic exercise ("exercise mimetic"). It is the **orally-bioavailable successor** to **SLU-PP-332 (#60)**, from the same laboratory, and is a **chemically distinct scaffold** built specifically to overcome #60's limitations. ## Mechanism (as proposed) the **estrogen-related receptors (ERRα/β/γ)** are **orphan nuclear receptors** — structurally related to estrogen receptors but **not activated by estrogens** — that act as master transcriptional regulators of **mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and the Krebs cycle**, and are **essential for skeletal-muscle adaptation to aerobic exercise.** SLU-PP-915 is a **pan-agonist** (hitting all three, with ERRα central to the effect) that **induces Ddit4** — a driver of the **acute aerobic-exercise transcriptional program** — and thereby increases **maximal exercise capacity** and **oxidative (type-IIa) muscle fibers.** The advance over #60 is purely **pharmacokinetic-chemical**: a **new scaffold** (boronic-acid thiophene) engineered from ERRγ crystal-structure data to be **orally absorbed** while preserving the same receptor pharmacology — so the *mechanism* is shared with #60, but the *deliverability* (in mice) is new.

Evidence grades by outcome:
outcome: Endurance / exercise capacity (the marketed use)
grade: F
base: Mouse studies: enhanced running distance/duration; oral efficacy (first for the class); Ddit4 induction; type-IIa fiber shift
caveat: Real, notable mouse data + oral breakthrough — but no human trials at all
outcome: Oral bioavailability (its whole point vs #60)
grade: B
base: Demonstrated oral activity; 7-day dosing without accumulation/tachyphylaxis
caveat: The genuine advance over #60 — in mice; says nothing about human PK/safety
outcome: Metabolic syndrome / heart failure / muscle atrophy / DMD
grade: F
base: Preclinical (Billon 2024; Circulation heart-failure work; aging/DMD models)
caveat: Interesting breadth, all animal/cell; none established
outcome: Human efficacy or safety
grade: F
base: None
caveat: Zero human data as of 2026
outcome: Doping / sport status
base: Detection methods under development (2026)
caveat: Being built into anti-doping before approval; class is prohibited-category

Legal status:
region: EU
status: Not FDA-approved (gray-market)
note: not an approved drug; investigational/research chemical. Not a cosmetic.

Cosmetic claims:

Note: The "exercise pill" that fixed its predecessor's fatal flaw — with a pill. SLU-PP-915 is the successor to SLU-PP-332 (#60), and its story is full of intrigue. Three threads: (1) it solves the exact defect that likely doomed #60 — it's the first ERR agonist that actually works orally (its predecessor had to be injected); (2) it's a chemically different molecule that hits the same effect at a lower dose — more efficient by design; (3) the intrigue thickens around it — anti-doping labs are already building detection tests before it's anywhere near humans, and its inventor holds a direct financial stake in companies developing ERR agonists. It's a small molecule, not a peptide — and, like #60, it has zero human data.
Status note: status: preclinical; the decisive event would be a first-in-human trial — none yet; watch Myonid/Pelagos ERR-agonist pipelines

Sources:
Billon C, Appourchaux K, Côté I, Burris TP. An orally active estrogen receptor–related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. J Pharmacol Exp Ther. 2026;393(1):103787 (the defining paper: oral activity, distinct scaffold, comparable efficacy at lower dose, Ddit4).
Billon C, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024 (class metabolic effects).
Avliyakulov NK, Sobolevsky T, Ahrens E. Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332… for Doping-Control Purposes. Drug Test Anal. 2026 (anti-doping detection).
Conflict-of-interest disclosure: SLU-PP-915 IP (Saint Louis University; Burris inventor); Burris stockholder in Myonid Therapeutics and Pelagos Pharmaceuticals. (No human data; not approved as of 2026.)