SLU-PP-332 (ERR agonist / "exercise mimetic")
SLU-PP-332 — the ERR-agonist "exercise mimetic": what the mouse data show, and the translation problem

Class: small_molecule
Synonyms: SLU-PP-332
a pan-ERR agonist (estrogen-related receptor α/β/γ)
an "exercise mimetic." Successor compound: SLU-PP-915 (orally-active next-gen). INCI: none
Function tags: metabolic
fat loss
endurance / performance
(preclinical:) mitochondrial biogenesis
cardiac protection
Overall evidence grade: F
WADA prohibited: yes
WADA note: Sport: WADA-prohibited — banned in competition (exercise-mimetic / metabolic-modulator category). Athletes face doping sanctions; metabolites are detectable.
Last updated: 2026-07-13

In brief: SLU-PP-332 is a small-molecule ERR (estrogen-related receptor) agonist — an "exercise mimetic" designed to switch on the muscle's aerobic-exercise gene program without exercise. In mice it does striking things: increased oxidative muscle fibers, fatty-acid oxidation, energy expenditure and treadmill endurance; reduced fat mass; improved insulin sensitivity; and cardiac protection against pressure-overload heart failure — essentially reproducing exercise's metabolic benefits pharmacologically. It is often mis-sold as a "peptide"; it is a small molecule. Two honest problems cap it: first, it has poor oral bioavailability — so much so that its own creators (the Burris lab) built a successor, SLU-PP-915, to fix this; second, it belongs to the "exercise mimetic" class, which has repeatedly failed to translate from impressive mouse data into approved human drugs. There are no human trials, and it is a WADA-banned substance in sport. Genuinely exciting biology; no human proof; a known PK flaw.

## Identity a **small synthetic molecule** (not a peptide) developed by **rational drug design** as an agonist of the **estrogen-related receptors (ERRα, ERRβ, ERRγ)** — orphan nuclear receptors that are **master regulators of mitochondrial metabolism and the exercise-responsive gene program** in muscle. By switching ERR on pharmacologically, SLU-PP-332 aims to **reproduce the transcriptional signature of aerobic exercise** in a pill — hence "exercise mimetic." ## Mechanism (as proposed) the **estrogen-related receptors (ERRα/β/γ)** are orphan nuclear receptors that act as **master transcriptional regulators of mitochondrial biogenesis, oxidative metabolism, and the gene program muscle activates in response to aerobic exercise**. SLU-PP-332 **binds and activates all three ERR isoforms**, transcriptionally switching on a broad set of **fatty-acid-oxidation and mitochondrial genes** — increasing **oxidative (slow-twitch) muscle fibers**, **energy expenditure** and **endurance**, and shifting fuel use toward fat. In effect it triggers an "**acute aerobic exercise response**" at the gene-expression level. The appeal is obvious (exercise's benefits without the exercise); the reality is that this is shown **in mice**, and the molecule's **poor oral bioavailability** limits how well it could even work as a human oral drug.

Evidence grades by outcome:
outcome: Fat loss / anti-obesity (metabolic syndrome)
grade: F
base: Billon 2024 (DIO & ob/ob mice): ↑energy expenditure, ↑fatty-acid oxidation, ↓fat mass, ↑insulin sensitivity
caveat: Compelling mouse-only data; no human efficacy; the marketed use rests entirely on rodents
outcome: Endurance / aerobic capacity
grade: F
base: Mouse: ↑treadmill endurance; ERRα-dependent acute aerobic-exercise response; ↑oxidative fibers
caveat: Real preclinical performance signal — but animal-only, and WADA-banned for exactly this reason
outcome: Mitochondrial biogenesis / cellular respiration
grade: F
base: Cell + mouse: upregulates DDIT4, enhances mitochondrial function
caveat: Mechanistically well-shown in models; not human-validated
outcome: Cardiac / other (heart failure, muscle regen, kidney/aging)
grade: F
base: Mouse: cardiac protection vs pressure overload; ERRα in muscle regeneration (FASEB 2025)
caveat: Early, model-specific; exploratory
outcome: Human efficacy or safety (any use)
grade: F
base: None — no human trials; poor oral bioavailability documented
caveat: The double gap: no human data and a known PK flaw that undermines oral use (hence the SLU-PP-915 successor)
outcome: Safety
base: Short rodent studies
caveat: No human safety data; banned in sport; chronic-use effects unknown

Legal status:
region: EU
status: Not FDA-approved (gray-market)
note: not approved anywhere; investigational research chemical / chemical probe. Not a cosmetic. Sold "research use only."

Cosmetic claims:

Note: The "exercise in a molecule" compound — and 5-Amino-1MQ's small-molecule twin, via a different mechanism. Three points define this entry: (1) like #59 it's a small molecule, not a peptide (though constantly mis-sold as one) — extending the non-peptide tier; (2) it's an "exercise mimetic" — an ERR agonist that switches on the muscle's aerobic-exercise gene program without exercise; (3) the mouse data are striking, but it carries two honest killers — poor oral bioavailability (its own lab built a successor to fix it) and membership in a field (exercise mimetics) with a long record of failing to translate to humans. Zero human trials.
Status note: the moving part is the successor SLU-PP-915 and any first-in-human work; re-check whether ERR-agonism reaches clinical trials

Sources:
Billon C, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. (the discovery/mechanism).
Billon C, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024 (the obesity/metabolic-syndrome mouse study).
Hampton/Sitaula/Billon, et al. Med-chem optimization of the SLU-PP series → SLU-PP-915. Eur J Med Chem. 2023; Billon 2026 (JPET) — orally-active successor.
Avliyakulov, et al. In-vitro metabolites of exercise mimetic SLU-PP-332 for doping control. Drug Test Anal. 2026 (WADA context).
Zhao (2024) review — exercise mimetics: promise vs consistent failure to translate. No human interventional data as of 2026.