Two experimental "exercise mimetic" molecules, one family, one question: which is better? The usual split says 332 for fat loss and 915 for endurance. The published mouse data says something more interesting — endurance is a tie, the fat comparison was never run, and the real difference between them is that one works by mouth and the other doesn't. Neither has a single human data point.
SLU-PP-332 and SLU-PP-915 come from the same research program — the Burris group, originally at Saint Louis University, now at the University of Florida — and both are synthetic small-molecule agonists of the estrogen-related receptors ERRα, ERRβ, and ERRγ. Despite being sold in peptide circles, neither is a peptide: 332 is an acylhydrazone (C₁₈H₁₄N₂O₂, ~290 Da, CAS 303760-60-3) and 915 is a thiophene carboxamide with a boronic-acid group (C₁₇H₁₃BFNO₃S, ~341 Da, CAS 2285432-92-8).
The "estrogen-related" name misleads: ERRs do not bind estrogen. They are orphan nuclear receptors that are constitutively active and regulate mitochondrial biogenesis, oxidative phosphorylation, and fatty-acid oxidation programs in muscle, heart, liver, and fat. An agonist turns up the volume on programs the body already runs during exercise — which is why both compounds get called "exercise mimetics."
332 was designed first, optimized from the earlier ERRβ/γ agonist GSK4716 by adding a naphthalene ring to gain ERRα activity. 915 came later, from a new thiophene series built off the ERRγ–GSK4716 crystal structure, with the acylhydrazide replaced and a boronic acid substituted for microsomal stability. The design goal for 915 was explicit: keep the pan-ERR activity and make it orally bioavailable.
The cleanest comparison comes from Hampton et al. 2023, which measured both compounds in the same cotransfection assay. Lower EC₅₀ means more potent — less compound needed to switch the receptor on halfway.
EC₅₀ at each ERR receptor (lower = more potent)
Hampton et al. 2023, Table 4 — both compounds, same assay. Toggle to see the second published set of 915 values.
332 is ~4.2× more potent than 915 at ERRα, ~1.9× at ERRβ, and essentially tied at ERRγ.
Three things to take from the numbers. First, the "332 has an ERRα advantage" claim is correct — 98 vs 414 nM, about a 4-fold difference, and within 332 itself the α preference is ~4.4-fold over γ. Second, the difference is modest: at ERRγ the two are effectively tied (428 vs 378 nM), so "915 has an ERRγ advantage" is not supported. Third, no study has shown that the 4-fold in-vitro α gap causes a divergent outcome in a live animal. In vivo, the two compounds mostly converge on the same endpoints — which is the first hint that the receptor-subtype story is not where the real difference lives.
Every claim in this article carries a label. ANIMAL/PRECLINICAL means mouse or rat studies. MECHANISTIC THEORY means cell or reporter assays, gene expression, or reasoning from mechanism. INFERENCE means a conclusion drawn across studies that no study directly tested. HUMAN means dosed in people — a label that appears exactly once in this article, in section 08, as an absence.
Primary papers: Billon et al., ACS Chemical Biology 2023 (exercise capacity) and Billon et al., Journal of Pharmacology and Experimental Therapeutics 2024 (metabolic syndrome). All in-vivo work is in male mice, from one research lineage, in small groups (n=6–8).
"12% weight loss" is wrong. It is 12% lower body weight than vehicle controls at day 28, in animals still gaining weight on a high-fat diet. "10× less fat" is fat gained during the study, not loss of 90% of existing fat. And in lean mice there was no weight change at all. The fat effect is prevention of gain, in an obese model — not fat loss. Section 06 goes through this in full.
Primary papers: Hampton et al., European Journal of Medicinal Chemistry 2023 (identification); Xu et al., Circulation 2024 (heart failure, head-to-head with 332); Billon et al., Journal of Pharmacology and Experimental Therapeutics 2026 (oral exercise mimetic, head-to-head with 332). Again: male mice only, one research lineage.
There is a head-to-head literature — two papers, not zero. Neither tested both compounds in an obesity or fat-loss model.
The pattern across all three: where the compounds differ in vivo, the difference is about timing in the heart model and oral bioavailability — not about receptor-subtype selectivity. The 4-fold in-vitro ERRα gap has never been shown to cause a divergent outcome in a live animal. Label: INFERENCE — unproven, and the head-to-heads point the other way.
The claim "332 is better for fat oxidation, metabolic adaptation, and body composition" splits into three parts with three different verdicts.
Fat oxidation: supported in mice. 332 raised fatty-acid oxidation ~25%, lowered respiratory exchange ratio within 2 hours of the first dose, and raised energy expenditure (Billon 2024, chow and obese mice). Label: ANIMAL/PRECLINICAL. But the mechanism — PDK4 induction shifting fuel use from glucose toward fat — is the same pathway 915 activates. Nothing in the data says 915 would not do this. The comparative part ("more interesting than 915") is untested, because 915 has never been tested for fat oxidation or fat mass in an obesity model. Label for the comparison: INFERENCE.
Metabolic adaptation and body composition: partially supported in mice, with major caveats. In obese mice: ~12% lower weight versus vehicle, ~5 g versus under 0.5 g of fat gained in 28 days, fasting glucose and insulin down, glucose tolerance improved — but lean mass unchanged, food intake unchanged, insulin tolerance unchanged, and in lean mice there was no weight change and no glucose-tolerance change at all. Male mice only, n=7–8 per group, single lab. Label: ANIMAL/PRECLINICAL.
Fat gained over 28 days — obese mice, Billon 2024
This is fat gained during the study — animals on a 60%-fat diet. It is not 90% of existing fat lost. Treated mice still gained weight; they gained ~12% less than controls.
The wording traps, stated once plainly: "mice lost 12% of their body weight" is wrong. "10× less fat" is fat gained, not fat lost. "Body composition improved" means less fat gained with lean mass unchanged — in obese male mice, at thermoneutral housing (30 °C, which suppresses brown-fat thermogenesis and is not normal mouse housing, let alone human conditions), from one lab, with no human data.
The claim "915 may have advantages for cardiovascular efficiency, mitochondrial function, and endurance" also splits three ways.
Cardiovascular efficiency: partially supported in one mouse disease model; "efficiency" is not the papers' word. In the Xu 2024 head-to-head, 915 improved ejection fraction from week 2 (332: weeks 4–6) and preserved stroke volume and cardiac output where 332 did not. But this is pressure-overload heart failure in mice, not healthy cardiovascular efficiency — no VO₂, blood-pressure, or exercise cardiac-output data exist. The hedged "may have advantages" is fair; "cardiovascular efficiency" implies a general fitness benefit that was never measured. Label: ANIMAL/PRECLINICAL.
Mitochondrial function: supported for 915 — and equally for 332; not a 915 advantage. 915 preserved isolated heart-mitochondria respiration (Xu 2024) and raised TFEB/autophagy genes in cells (Losby 2024). But 332 also raised muscle mitochondrial respiration and biogenesis and mtDNA (Billon 2023) and mitigated cardiac mitochondrial ultrastructural damage (Xu 2024). No head-to-head mitochondrial comparison favors 915, and the cardiac mechanism is ERRγ-mediated for both. Label: ANIMAL/PRECLINICAL + MECHANISTIC THEORY.
Endurance: overstated as a 915 advantage — contradicted as a superiority claim. Billon 2026, direct comparison: injected 915 ≈ injected 332, both ~50% better than vehicle. Hampton 2023: 915 alone beat vehicle. No study shows 915 beats 332 on endurance. 915's genuine endurance-relevant advantage is that it works orally (32 mg/kg twice daily, 7 days, comparable to injection) while 332 does not — and at a lower mg/kg injected dose. Presenting endurance as a 915 win misreads the head-to-head. Label: ANIMAL/PRECLINICAL (head-to-head).
Endurance was tested for both compounds (treadmill to exhaustion, mice). But it was tested in sedentary, untrained, male mice, in small groups (n=6), over 7 days (332) or acutely/7 days (915). No VO₂max, no trained animals, no humans. And every in-vivo efficacy paper above used male mice — the only female-derived data are cultured cells (Bonanni 2025, section 08). Sex-generalized claims are unsupported.
Established human dose for either compound: none. No human pharmacokinetics, no human dose-ranging, no Phase 1. All published doses are mouse doses, mostly by injection: 332 — 25–50 mg/kg injected once or twice daily; 915 — 20 mg/kg injected, 25 mg/kg injected twice daily (heart model), 32 mg/kg oral twice daily (7 days). Oral bioavailability in humans is unmeasured for both. Mouse doses cannot be converted to human doses by body weight — and 332 is stated by its developers to lack oral bioavailability in mice, which undercuts the oral 332 products sold online.
Toxicity — what is actually known (short-term mouse only): "No overt toxicity" is the recurring phrase — Billon 2023 (50 mg/kg twice daily injected, 10 days; normal blood counts, electrolytes, creatine kinase); Xu 2024 (25 mg/kg twice daily injected, 6 weeks, both compounds; no overt toxicity, but no full adverse-event table); Billon 2024 (no liver-enzyme rise in obese mice, 28 days). That is not a safety profile: no chronic toxicology, carcinogenicity, reproductive, or genotoxicity study is published for either compound, and no human adverse-event data exist at any dose.
Long-term and off-target risks: unknown. ERRs are expressed in heart, skeletal muscle, liver, kidney, brain, and fat and regulate broad transcriptional programs; chronic systemic pan-ERR activation above an already-high constitutive baseline is uncharacterized. Theoretical concerns raised in the literature: ERRα is implicated in metabolic reprogramming in several cancers — oncologic risk of chronic agonism is untested; the balance of ERRα versus ERRγ activity "may be important to avoid potential side effects" (Billon 2024, Discussion); 915's boronic-acid group can in principle bond covalently to non-target proteins (flagged in a 2026 review — a chemistry caution, not a demonstrated toxicity); PDK4-mediated inhibition of glucose use is a hypothesized risk raised by commentators, not a measured outcome. None of these is a demonstrated harm; equally, none has been excluded. Label: MECHANISTIC THEORY / INFERENCE.
Clinical development status: no registered clinical trial for either compound. ClinicalTrials.gov was queried directly by exact name on November 7, 2026 — zero studies for SLU-PP-332 and zero for SLU-PP-915. No FDA or EMA approval for any indication; no publicly disclosed IND. The papers position the compounds as "promising agents" and "valuable chemical tools" for metabolic disease, heart failure, sarcopenia, and muscular dystrophy — preclinical candidates, not drugs in development in the public record.
Anti-doping: WADA's 2027 Prohibited List (published September 21, 2026, in force January 1, 2027), §S4.4.1 metabolic modulators, names "SLU-PP-332, SLU-PP-915 and related substances", prohibited at all times, non-Specified Substances. The 2026 list did not name them; they were caught by the S0 non-approved-substances catch-all. Doping-control labs published human-liver-metabolism and mass-spectrometry detection methods for both in 2026.
The only human-derived datum: Bonanni et al., Frontiers in Physiology 2025 — muscle cells cultured from biopsies of 10 physically inactive women undergoing hip surgery, treated with 10 µM SLU-PP-332 for 48 hours: oxidative-stress and senescence markers down; SIRT1, PGC-1α, ERRα, and myotube formation up. Label: human cells ex vivo — not human efficacy, not a dose, not a trial. (Verified via secondary summaries; confirm details from the primary paper before citing it as "human data.")
Essentially all in-vivo work on both compounds is the Burris group and collaborators (Saint Louis University / Washington University / University of Florida, plus Baylor and Salk for Xu 2024). No independent replication group has published in-vivo efficacy for either compound. The senior author is reported in secondary summaries to be an inventor with equity in companies developing ERR agonists — verify against the papers' disclosure statements before asserting it in print. That concentration does not make the data wrong; it makes independent replication the missing piece.
"Which one is better?" has no answer in humans — and in mice the answer depends on the endpoint: fat and metabolic outcomes, only 332 tested; heart-failure timing, 915 earlier; endurance, a tie; oral use, 915 only. The published difference that matters most is route, not receptor subtype: 332 lacks oral bioavailability and all its mouse work is by injection; 915 was engineered to be orally active in mice. The 4-fold ERRα potency gap is real in a dish and has never been shown to drive a different outcome in a live animal.
The one-sentence version: Two experimental ERR agonists with real but mouse-only evidence — 332 for fat-gain prevention and endurance by injection, 915 for the same endurance by mouth plus earlier cardiac benefit — and no human data, no human dose, and no approval for either.