SLU-PP-332: Scientific Profile
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SLU-PP-332 (CAS 303760-60-3) is a non-peptide pan-ERR agonist (ERRα/β/γ) of the acylhydrazone class, an exercise mimetic for research; it induces mitochondrial biogenesis via PGC-1α. Preclinical use / RUO.
SLU-PP-332 is a synthetic non-peptide molecule classified as a pan-ERR agonist (estrogen-related receptors), with activity on all three isoforms: ERRα (EC50 ~98 nM), ERRβ (EC50 ~230 nM), and ERRγ (EC50 ~430 nM). It belongs to the acylhydrazone class (IUPAC: 4-hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide; CAS 303760-60-3; formula C18H14N2O2; molecular weight 290.32 g/mol). It was developed at Saint Louis University by the Burris group. ERRs are constitutively active orphan nuclear receptors that, together with PGC-1α, regulate the transcription of genes involved in mitochondrial biogenesis and oxidative metabolism; for this reason SLU-PP-332 is used as an exercise-mimetic research tool. In vitro and preclinical applications: mitochondrial biogenesis, fatty acid oxidation, and energy metabolism. The primary characterization is described in Billon et al., ACS Chemical Biology 2023;18(4):756-771. Reconstitution: dissolve in DMSO for in vitro stock solutions. Storage: powder at -20 °C protected from moisture and light. For research (RUO).
Mechanism of action
SLU-PP-332 acts as an allosteric agonist of all three members of the ERR subfamily (ERRα/NR3B1, ERRβ/NR3B2, ERRγ/NR3B3), increasing their constitutive transcriptional activity without requiring an endogenous ligand (the ERRs lack an identified natural ligand). Activation recruits PGC-1α/β coactivators to ERRE response elements in the promoters of mitochondrial genes: NRF1, TFAM, MCAD, CPT1B, UCP3, cytochrome c, ATP synthase and Krebs cycle enzymes. The result is increased mitochondrial biogenesis, mitochondrial density in type I/IIa skeletal muscle, oxidative capacity and aerobic ATP production. In white adipose tissue, it induces a partial "browning" program with UCP1 expression and adaptive thermogenesis. In hepatocytes, it increases fatty acid β-oxidation and reduces de novo lipogenesis. In murine models, doses of 12.5 mg/kg/day for 4 weeks increase VO2max ~70% and time to fatigue 50%. EC50 on ERRα: ~98 nM. Plasma half-life in mouse: ~3 hours. Oral bioavailability: ~40%. Hepatic CYP3A4 metabolism.
Mechanism summary
Non-peptide pan-ERR agonist with activity on ERRα (EC50 ~98 nM), ERRβ (~230 nM) and ERRγ (~430 nM). In concert with PGC-1α it activates the transcriptional program of mitochondrial biogenesis and oxidative metabolism, reproducing features of the exercise phenotype in preclinical models.
Estudios Clínicos (9)
- A Synthetic ERR Agonist Alleviates Metabolic Syndrome (Banerjee S, Billon C, Banerjee O, et al. · Journal of Pharmacology and Experimental Therapeutics · 2024) — Estudio en ratones C57BL/6 con dieta alta en grasa tratados con SLU-PP-332 12.5 mg/kg/día por 6 semanas. PMID 37739806.
- SLU-PP-332 induces an aerobic exercise response and endurance capacity (Billon C, Sitaula S, Banerjee S, et al. · ACS Chemical Biology · 2023) — Characterization of the first synthetic pan-ERR agonist in murine models, evaluating aerobic capacity, mitochondrial gene expression, and exercise-like response. PMID 36988910.
- Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. (Xu W, et al. · Circulation · 2024) PMID 37961903.
- Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. (Wang XX, et al. · Am J Pathol · 2023) PMID 37717940.
- Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. (Bonanni R, et al. · Front Physiol · 2025) PMID 40692696.
- Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling. (Okda HE, et al. · Int J Biol Macromol · 2026) PMID 41850449.
- [Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications]. (de Souza-Lima J, et al. · Rev Med Chil · 2026) PMID 42024694.
- Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes. (Avliyakulov NK, et al. · Drug Test Anal · 2026) PMID 41688415.
- In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. (Möller T, et al. · Rapid Commun Mass Spectrom · 2026) PMID 41588687.
Warnings
SLU-PP-332 is a compound exclusively for research use (RUO); the following warnings and handling considerations apply to its use in the laboratory:
- Experimental compound without clinical studies in humans
- Long-term safety profile unknown
- Possible effects on cardiac function due to ERRγ activation
- Potential drug interactions via CYP3A4
- Limited data on carcinogenicity and mutagenicity
- Do not use outside validated research protocols
- Models with known hypersensitivity to SLU-PP-332 or excipients
- Pregnant or lactating models (insufficient data)
- Models under 18 years old
- Models with decompensated heart failure
- Models with severe hepatic or renal insufficiency
- Models with pre-existing mitochondrial myopathies
Technical data
- CAS
- 303760-60-3
- Molecular formula
- C18H14N2O2
- Molecular weight
- 290.32 Da
- Compound type
- peptide
- Storage
- -20°C protegido de luz.
- Shelf life (lyophilized)
- 24 months at -20°C
- Shelf life (reconstituted)
- 7 days at 4°C in DMSO
- Light-sensitive
- Sí
Frequently asked questions about SLU-PP-332
What is SLU-PP-332?
SLU-PP-332 (CAS 303760-60-3) is a non-peptide pan-ERR agonist (ERRα/β/γ) of the acylhydrazone class, an exercise mimetic for research; it induces mitochondrial biogenesis via PGC-1α. Preclinical use / RUO.
What is the mechanism of action of SLU-PP-332?
Non-peptide pan-ERR agonist with activity on ERRα (EC50 ~98 nM), ERRβ (~230 nM) and ERRγ (~430 nM). In concert with PGC-1α it activates the transcriptional program of mitochondrial biogenesis and oxidative metabolism, reproducing features of the exercise phenotype in preclinical models.
What is SLU-PP-332 researched for?
In preclinical research, SLU-PP-332 is studied mainly in: research on endurance performance; models of mitochondrial biogenesis; studies of lipid oxidation. Material exclusively for scientific research.
What are the chemical properties of SLU-PP-332?
Molecular formula C18H14N2O2; molecular weight 290.32 Da; CAS number 303760-60-3.
How is SLU-PP-332 stored?
Condiciones de conservación: -20°C protegido de luz.; estabilidad liofilizado: 24 meses a -20°C; una vez reconstituido: 7 días a 4°C en DMSO; protéjase de la luz.
What routes of administration are studied for SLU-PP-332?
In the research models the following are described: Oral, Subcutaneous. Use is exclusively for scientific research.