SLU-PP-332

SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors ERRα, ERRβ, and ERRγ. It was developed by the Thomas Burris laboratory at Saint Louis University and Washington University in St. Louis. Pharmacology is characterized in cell-based assays and rodent models. As of May 2026, no published human pharmacokinetic, safety, or efficacy data exists.

The molecule has a naphthalene scaffold derived from an earlier aniline-based ERR-agonist series. Molecular weight is approximately 367 g/mol. CAS number is 303760-60-3. The Saint Louis University name reflects the original research site (now relocated with Burris's lab moves).

The Burris Lab Origins

The Burris group has worked on nuclear receptor pharmacology for two decades. The first paper describing SLU-PP-332 was Billon et al., ACS Chemical Biology, 2023. The compound was designed by structure-based optimization of an earlier ERR-agonist scaffold, with a naphthalene substituent replacing an isopropyl phenyl group. Molecular modeling predicted, and crystal-structure analysis confirmed, π-π stacking interactions with phenylalanine residues in the ERRα ligand-binding domain that gave it the highest potency at this isoform.

In cell-based cotransfection assays, EC50 values are 98 nM at ERRα, 230 nM at ERRβ, and 430 nM at ERRγ. The compound is described as a pan-agonist with roughly 4-fold ERRα selectivity over ERRγ.

The Preclinical Story

Four lines of mouse evidence support the "exercise mimetic" framing:

Skeletal muscle and endurance (Billon 2023): SLU-PP-332 at 50 mg/kg intraperitoneal, twice daily, increased type IIa oxidative skeletal muscle fibers and treadmill endurance in sedentary mice. The transcriptional program induced was ERRα-dependent and overlapped substantially with the gene-expression changes seen after acute aerobic exercise. DDIT4 was identified as a key induced gene.

Metabolic syndrome (Billon 2024 in J Pharmacol Exp Ther): In diet-induced obese mice and ob/ob mice, 50 mg/kg twice daily for 28 days (12 days for ob/ob) decreased fat mass, increased energy expenditure, increased fatty acid oxidation, and improved insulin sensitivity. The reductions in fat mass were on the order of 25-30 percent without exercise, which is large for a preclinical metabolic agent.

Cardiac protection (Xu et al., Circulation, 2024): In a transaortic constriction (TAC) mouse model of pressure-overload heart failure, SLU-PP-332 improved ejection fraction, reduced cardiac fibrosis, and restored mitochondrial ultrastructure over 6 weeks. The effect was mediated primarily by ERRγ activation. The compound did not prevent cardiac hypertrophy itself, only the metabolic and functional decline. A structurally distinct sister compound, SLU-PP-915, produced similar effects.

Aging kidney (Wang et al., American Journal of Pathology, 2023): In aged mice, ERR agonism with SLU-PP-332 reduced albuminuria, preserved podocin expression, and restored mitochondrial function in kidney tubules. The effect was anti-inflammatory and partially anti-fibrotic.

The translation gap from these mouse results to humans has not been tested.

Regulatory and Sport Status

SLU-PP-332 has no marketing approval anywhere. It is sold as a research chemical by laboratory-supply companies (Cayman Chemical, MedChemExpress, Tribioscience) and as an oral tablet or injectable powder by research-peptide vendors. None of these are pharmaceutical-grade products approved for human use.

The anti-doping situation is the most actionable data point for athletes. A February 2026 paper in Drug Testing and Analysis characterized SLU-PP-332's in vitro metabolites specifically for sport doping control. The fact that anti-doping laboratories have already invested in detection methodology indicates the substance is in scope for testing, even if not explicitly named on the current Prohibited List. The closest WADA-banned analog is SR9009 (Stenabolic), a REV-ERB agonist exercise mimetic, which falls under Section S4.1.2 "Other modulators of metabolism". The same provision covers metabolic modulators that mimic exercise adaptation. Athletes subject to WADA, USADA, or sport-federation testing should treat SLU-PP-332 as a probable in-competition and out-of-competition prohibited substance.

This compound is likely covered by the WADA Prohibited List under Section S4 (Hormones and Metabolic Modulators). Use in competitive sport, in-competition or out-of-competition, may constitute an anti-doping rule violation.

The compound is not on the FDA, EMA, or any other major drug agency's approval pathway. No commercial pharmaceutical sponsor has filed an IND application as of public records.

ERRα, ERRβ, and ERRγ are nuclear receptors classified as orphan because no endogenous ligand has been definitively identified. They are constitutively active transcription factors that regulate metabolic gene expression in skeletal muscle, heart, kidney, brown adipose tissue, and brain. The receptors share a coactivator with PGC-1α, the master regulator of mitochondrial biogenesis.

When SLU-PP-332 binds the ERR ligand-binding domain, it stabilizes a conformation that increases coactivator recruitment and transcriptional output. Downstream effects in muscle include:

• Upregulation of mitochondrial-biogenesis genes including NRF1, NRF2 (nuclear respiratory factors), and mitochondrial DNA-encoded electron transport chain components
• Upregulation of fatty acid oxidation genes including CPT1B (carnitine palmitoyltransferase 1B), MCAD (medium-chain acyl-CoA dehydrogenase), and PDK4
• Increase in type IIa (fast oxidative) muscle fiber content at the expense of type IIb (fast glycolytic)
• Induction of DDIT4, a key transcriptional response gene to acute exercise

In cardiac tissue, the dominant mechanism shifts to ERRγ. The Xu 2024 Circulation paper showed that genetic ERRγ deletion abolished the cardioprotective effect, while ERRα deletion had less impact.

The compound's pharmacokinetics in mice are sufficient for in vivo dosing: plasma and muscle exposure at 0.2 μM and 0.6 μM respectively, 6 hours after 50 mg/kg intraperitoneal injection. Oral bioavailability has been described as sufficient for in vivo studies, with the compound used either orally or intraperitoneally in published work. Human pharmacokinetic data is not published.

In mouse models:

• Increased treadmill endurance and capillary density in skeletal muscle (Billon 2023)
• 25-30 percent reduction in fat mass in diet-induced obese mice over 28 days, without exercise (Billon 2024)
• Improved cardiac ejection fraction and reduced fibrosis in TAC heart failure (Xu 2024)
• Reduced albuminuria and restored mitochondrial function in aging kidney (Wang 2023)
• Reduced inflammation markers and mitochondrial damage in aged tissues

In humans: zero published controlled data.

User reports from research-chemical communities describe subjective increases in workout capacity, faster recovery, and minor fat-mass changes over weeks of oral dosing. These are anecdotal and not from controlled trial. The same population is using the compound at doses that have not been validated against any pharmacokinetic measurement in humans.

Worth noting: the mouse fat-mass reductions occurred without exercise. The exercise-mimetic framing is mechanistic and based on transcriptional signature, not on a comparison of running mice with and without the drug. Whether the same effect happens in active human users at much lower exposure levels is unknown.

Published mouse-study doses are 50 mg/kg intraperitoneal, once or twice daily, for 12 to 28 days. This is the dose used across the four primary preclinical papers (Billon 2023, Billon 2024, Xu 2024, Wang 2023).

For a 70 kg human, naïve allometric scaling from a 25 g mouse using the standard body-surface-area conversion (mouse Km factor 3, human Km factor 37) gives an equivalent dose of approximately 4 mg/kg, or 280 mg per day. This calculation is not a recommended dose. It is a heuristic showing that biohacking community oral protocols (typically 250 mcg to 1.5 mg, or one 50 mg vendor tablet, per day) are orders of magnitude below the active mouse dose.

The disconnect is large enough that one of two things must be true. Either the human protocols are subtherapeutic and any reported subjective effect is placebo or context. Or the bioavailability and target engagement in humans differ substantially from the rodent reference data. Neither possibility has been formally tested.

No standardized human dosing protocol exists for SLU-PP-332. The published mouse doses cannot be assumed safe in humans without bridging pharmacokinetic data, and that data does not exist.

Mouse safety data (Billon 2023, 2024 and Xu 2024) shows the compound was tolerated at 50 mg/kg intraperitoneal twice daily over the 12-28 day study periods without overt signs of toxicity. Body weight in non-obese controls was unaffected. Cardiac function in healthy mice was unchanged. No mortality was reported.

Human safety data: none.

Theoretical concerns worth flagging:

• Off-target nuclear receptor effects: ERRs share structural similarity with estrogen receptors (ERα, ERβ), and the original Burris-lab compounds were designed in part for ERR selectivity. The selectivity for ERRs over ERs is high in published assays but has not been characterized in human tissue panels.
• Cardiac arrhythmia risk: ERRγ activation in heart tissue produces favorable metabolic remodeling in failure models but the effect in healthy hearts at chronic high exposure has not been studied. Acute mitochondrial-function changes in cardiomyocytes can be arrhythmogenic.
• Cancer biology: ERR signaling is implicated in metabolic reprogramming of some tumors, particularly breast cancers expressing ERRα. The implications of agonism rather than inhibition in patients with occult or active malignancy are unresolved.
• Drug interactions: not characterized. CYP450 metabolism profile has been partially studied (the 2026 metabolite paper for doping control includes hepatic microsome data) but interaction studies with common medications are absent.
• Long-term effects: zero data beyond 28 days in any species.

The bottom line on safety: at the dose levels used in vendor-sold oral protocols, acute toxicity is likely low because exposure is likely sub-pharmacological. At the dose levels that produced mouse effects, no human safety data exists at all.

SLU-PP-332 is mechanistically grouped with other exercise-mimetic compounds. The closest analog is AICAR (an AMPK activator). AICAR and ERR agonists converge on PGC-1α activation downstream, but enter the pathway through different receptors. SR9009 (REV-ERB agonist) is another structurally distinct exercise-mimetic class. Both AICAR and SR9009 are explicitly WADA-banned. SLU-PP-332 has not been individually named on the list but operates in the same regulatory zone.

The pairing with 5-Amino-1MQ targets a different metabolic node: 5-Amino-1MQ inhibits NNMT (nicotinamide N-methyltransferase), increasing intracellular NAD+ and SAM. Combining with an ERR agonist would theoretically pair an upstream substrate increase with a downstream transcriptional activation. No animal or human study of the combination has been published.

The pairing with NAD+ precursors (NMN, NR) is mechanistically reasonable: ERR agonism activates the transcriptional program of mitochondrial biogenesis, NAD+ supplies the substrate for the resulting sirtuin and ETC activity. Untested as a combination in humans or in mice.

The pairing with MOTS-c addresses a different layer of mitochondrial regulation. Both are early-stage compounds with substantially different evidence profiles: MOTS-c has small-scale human data, SLU-PP-332 has none.

The pairing SLU-PP-332 should not be in is with competitive sport. The 2026 metabolite-identification paper is a signal that anti-doping laboratories consider this compound in scope. Athletes under any WADA, USADA, or federation testing program face material anti-doping risk from this compound, even if it is not explicitly named on the current Prohibited List.

For informational and educational purposes only. Not medical advice. Not for human consumption unless prescribed by a licensed physician for an FDA-approved indication. Consult a qualified healthcare provider before using any peptide or pharmaceutical product.