slu-pp-332

small-molecule pan-ERR agonist marketed as 'exercise in a pill'. real, reproducible mouse data on endurance and fat oxidation. zero human trials, and the molecule itself is not even orally bioavailable.

tier C · weight loss · ERR pan-agonist · preclinical

verdict

a small molecule, not a peptide. a synthetic pan-ERR agonist that switches on the same oxidative-metabolism gene program as endurance exercise in mice. preclinical only, no human data, poor oral bioavailability.

if you're asking what the human evidence looks like — there isn't any. zero registered clinical trials, zero human pharmacokinetic data, zero human safety dataset, zero human efficacy. every endurance, fat-loss, heart and kidney result comes from mice, cell lines, or one ex vivo human-muscle pilot. the compound is at the stage where 'does this do anything in people' has not been asked in a trial, let alone answered.

if you're asking about the 'exercise in a pill' framing — earned at the level of biology, oversold at the level of outcome. in skeletal muscle SLU-PP-332 turns on an ERRα-dependent acute-exercise gene program (the same signature a bout of running produces), and sedentary mice given it ran meaningfully longer and farther than controls. but the mimicry is metabolic and oxidative. it does not reproduce strength, the full cardiovascular conditioning response, tendon and bone loading, or the systemic effects of training, and none of it has been shown in a human.

if you arrived through a vendor selling it as a capsule or 'peptide' — two problems. first, it is not a peptide. it is a small-molecule acylhydrazone (C18H14N2O2, about 290 Da). second, the peer-reviewed work is explicit that SLU-PP-332 lacks oral bioavailability, which is the entire reason the same lab had to build a separate oral analog, SLU-PP-915. an oral capsule of 332 is selling the form the research specifically had to engineer around.

based on published preclinical evidence. not medical advice. an unapproved research compound with no human data.

why C-tier

C-tier because the mechanism is well-described in the peer-reviewed literature and the preclinical mouse data is reproducible, while the human evidence base is entirely absent: zero trials, zero human pharmacokinetics, zero human safety data. a plausible, well-characterized mechanism with no human data is what C-tier describes. not D-tier because nothing here has failed: the chemistry and the academic work are legitimate, there is no published carcinogenicity signal (the way there is for the older exercise mimetic GW501516, which reached humans and was abandoned), and the compound is untested in humans rather than tested and found wanting. not B-tier because B needs either emerging human data, which does not exist, or unusually strong and independently replicated preclinical evidence, and most of the work comes from one cluster of labs with the molecule still not orally usable.

the core tension

SLU-PP-332 is the cleanest version of a recurring story: a legitimate academic mechanism that escapes into the research-chemical market long before the science is ready for people. The biology is real. ERRs are the transcription factors through which PGC-1α runs the mitochondrial program, and a single bout of running and a dose of SLU-PP-332 light up an overlapping gene signature. The mouse outcomes (endurance, fat oxidation, metabolic-syndrome reversal, cardioprotection, kidney aging) are reproduced across the originating lab's papers. But the entire case is preclinical: zero human trials, zero human pharmacokinetics, zero human safety data, and most of the evidence comes from one cluster of collaborating labs without broad independent replication. The molecule is not even orally bioavailable, which is why a separate oral successor (SLU-PP-915) had to be made. Where the published research supports a claim, the report below states it. Where the evidence stops at mice, it says so.

what it is

SLU-PP-332 is a small-molecule synthetic agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ), a family of orphan nuclear receptors that govern mitochondrial biogenesis and oxidative metabolism. It is not a peptide, despite being sold alongside them: it is an acylhydrazone, molecular formula C18H14N2O2, about 290 Da, derived by optimizing the older ERR-agonist scaffold GSK4716. It is most potent at ERRα (cell-based EC50 about 98 nM), with weaker activity at ERRβ and ERRγ. It does not activate the classical estrogen receptors.

what it does

ERRs are the transcription factors through which the exercise-induced coactivator PGC-1α runs its mitochondrial program: oxidative phosphorylation, the TCA cycle, fatty-acid oxidation, mitochondrial biogenesis. By activating ERRs directly, SLU-PP-332 switches that program on without the exercise. In mice it induced an ERRα-dependent acute-aerobic-exercise gene signature in muscle, increased oxidative (type IIa) fibers and mitochondrial content, and in the foundational study sedentary animals ran roughly 70% longer and 45% farther than vehicle controls. In diet-induced-obese mice dosed by injection for four weeks, the metabolic-syndrome study reported reduced fat-mass accumulation, higher energy expenditure and fatty-acid oxidation, and improved glucose tolerance, without a reduction in food intake. All of it is animal or cell data.

origin

developed in the Thomas Burris laboratory (Saint Louis University, with University of Florida and Washington University collaborators) as a chemical probe to ask whether activating ERR pharmacologically could mimic exercise. The foundational paper is Billon et al., ACS Chemical Biology (2023). Follow-on papers extended it to metabolic syndrome (J Pharmacol Exp Ther 2024), heart failure (Circulation 2023, mediated mainly by ERRγ), and the aging kidney (Am J Pathol 2023). A biotech, Pelagos Pharmaceuticals, has been reported as working toward clinical development, with no registered trial and no announced timeline as of 2026.

why researchers are interested

the mechanism is legitimate and unusually clean: ERRs really are the effector arm of the PGC-1α exercise program, and SLU-PP-332 really does reproduce that transcriptional signature in muscle. the mouse endurance and fat-oxidation effects are striking on paper, the compound has no published carcinogenicity signal (unlike the older 'exercise mimetic' GW501516, which reached humans and was abandoned for cancer), and the 'exercise in a pill' story is irresistible to a market built on shortcuts. that is the appeal. it is also the trap: a clean mouse mechanism is the starting line of drug development, not the finish.

does it work

in mice, the oxidative and endurance effects are real and reproduced across several of the lab's studies. in humans, the evidence column is empty: no trials, no pharmacokinetics, no safety data, no efficacy. most of the work comes from a single cluster of collaborating labs, so even the preclinical case has had limited independent replication. and the molecule is not orally bioavailable, so the route that produced the mouse results (injection) is not the route a consumer product implies. the honest read is that SLU-PP-332 is a promising research probe whose human story has not started.

key facts

• molecular formula: C18H14N2O2
• molecular weight: about 290.3 Da (PubChem CID 5338394)
• amino acids: not a peptide; an acylhydrazone, 4-hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide
• half-life: not formally reported in the primary literature; circulating vendor half-life figures have no peer-reviewed basis
• type: small-molecule synthetic pan-ERR (ERRα/β/γ) agonist; not a peptide despite being sold alongside them
• CAS: 303760-60-3 (synonym SR9861)
• 0 registered human clinical trials
• 98 nM ERRα potency (cell-based EC50)
• ~45% farther run by sedentary mice vs vehicle (Billon 2023)
• i.p. route in mouse studies; not orally bioavailable

frequently asked questions

What is SLU-PP-332?

SLU-PP-332 is a small-molecule synthetic pan-agonist of the estrogen-related receptors (ERRα/β/γ), developed in the Burris lab as a research tool to test whether activating ERR could mimic the metabolic effects of exercise. It is not a peptide; it is an acylhydrazone (C18H14N2O2, about 290 Da). It has reproducible exercise-mimetic and metabolic effects in mice and no published human trial data.

Is SLU-PP-332 a peptide?

No. It is a small molecule, an acylhydrazone with the formula C18H14N2O2 and a molecular weight of about 290 Da. It has no amino-acid backbone. It is frequently mislabeled a 'peptide' because it is sold through the same research-chemical channels as peptides.

Is SLU-PP-332 an 'exercise in a pill'?

Only in a narrow, mechanistic sense, and not in humans. In mice it activates the same ERR/PGC-1α oxidative-metabolism gene program that endurance training switches on, and it increased running endurance in sedentary animals. It does not reproduce the strength, cardiovascular-conditioning, or systemic effects of real exercise, and no human study has tested any of it. The phrase is marketing, not a demonstrated human outcome.

Does SLU-PP-332 work for fat loss?

In diet-induced-obese mice, the metabolic-syndrome study reported reduced fat-mass accumulation and higher fatty-acid oxidation without reduced food intake. Those are animal results at injected doses. There is no human fat-loss data, and the compound is not orally bioavailable, so consumer-style oral use is not supported by the research.

Is SLU-PP-332 safe?

Unknown in humans. Short mouse studies reported no overt toxicity (normal blood counts and electrolytes, no rise in a muscle-damage marker), but there is no human safety data and no long-term, reproductive, or carcinogenicity testing. Broad activation of ERRs across the heart, liver, and kidney is a theoretical safety question that has not been resolved.

Is SLU-PP-332 FDA approved?

No. It has no approval for any use and is not in any registered human trial. It is sold under research-chemical labeling. It is also a prohibited substance class in sport (metabolic modulators / exercise mimetics), and anti-doping laboratories have already published methods to detect it.

related peptides

• slu-pp-915 — the orally bioavailable successor to 332, built by the same lab to fix the absorption problem
• 5-amino-1mq — another metabolic small molecule sold as a 'peptide' with reproducible mouse data and no human trials
• mots-c — mitochondrial / metabolic peptide in the same preclinical-to-thin-human-data space
• retatrutide — the metabolic compound with actual large human trials, for the contrast

reptides grades the research record and cites the literature behind every call. research reference only; not medical advice.