Additional Research Compound · For laboratory research use only
Also known as SLU PP 332, SLUPP-332, ERR agonist
SLU-PP-332 (4-hydroxy-N'-(naphthalen-2-ylmethylidene)benzohydrazide) is a synthetic small-molecule agonist of the estrogen-related receptors ERRα, ERRβ and ERRγ, orphan nuclear receptors that regulate mitochondrial and oxidative metabolism. It was described in 2023 as a pan-ERR agonist with the highest potency at ERRα and with pharmacokinetic properties suitable for use as an in vivo chemical tool1.
Published research is preclinical: a skeletal muscle cell line and mice1, mouse models of obesity2, aged mouse kidney3, a mouse pressure overload heart model4 and primary human myoblasts in culture5. Several authors from the originating group have declared holdings in companies developing ERR-targeted compounds1,6. Recent work addresses structure-activity relationships of the scaffold and in vitro metabolite identification for doping control6,7,8.
As described in the research literature
As described in the research literature, SLU-PP-332 increased mitochondrial function and cellular respiration in a skeletal muscle cell line, and in mice it was associated with an increase in type IIa oxidative muscle fibres and with an ERRα-dependent acute aerobic exercise gene programme1. On this basis the authors described it as an exercise mimetic1,2.
In the mouse heart, transcriptional activation of fatty acid metabolism and mitochondrial genes by SLU-PP-332 and a second agonist, SLU-PP-915, was shown by genetic dependency experiments to be mediated mainly through ERRγ4. In aged mouse kidney, the effects of the agonist were linked to the cGAS-STING and STAT3 signalling pathways3. A 2026 structure-activity analysis identified structural determinants of ERRα and ERRγ agonism, transcriptional efficacy and physicochemical properties across the scaffold6.
What published studies have examined
In mice, exercise endurance, muscle fibre type and gene expression were measured, and the dependence of the response on ERRα was tested1. Primary myoblasts from muscle biopsies of physically inactive women undergoing hip arthroplasty were treated in culture and examined for NOX4, SIRT1, PGC-1α, ERRα and FNDC5 expression, oxidative stress markers and myotube formation5.
Diet-induced obese and ob/ob mice were used to measure energy expenditure, fatty acid oxidation, fat mass accumulation and insulin sensitivity2.
Sources [2]
In 21-month-old mice, albuminuria, podocyte loss, mitochondrial function and inflammatory cytokines were examined in an eight-week study and compared with caloric restriction3. In a pressure overload model of heart failure, ejection fraction, fibrosis and survival were measured alongside RNA sequencing and metabolomics4.
Two 2026 studies characterised the compound by liquid chromatography-high resolution mass spectrometry and identified its in vitro metabolites using human liver S9 fractions and microsomes, with nine and 22 metabolites reported respectively7,8.
Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.
Billon C, Sitaula S, Banerjee S, et al. ACS Chemical Biology, 2023.
A Synthetic ERR Agonist Alleviates Metabolic Syndrome.
Billon C, Schoepke E, Avdagic A, et al. The Journal of Pharmacology and Experimental Therapeutics, 2024.
Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.
Wang XX, Myakala K, Libby AE, et al. The American Journal of Pathology, 2023.
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.
Xu W, Billon C, Li H, et al. Circulation, 2024.
Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study.
Bonanni R, Falvino A, Matticari A, et al. Frontiers in Physiology, 2025.
Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling.
Okda HE, Zhao P, Hayes M, et al. International Journal of Biological Macromolecules, 2026.
In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential.
Möller T, Krug O, Thevis M Rapid Communications in Mass Spectrometry, 2026.
Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes.
Avliyakulov NK, Sobolevsky T, Ahrens E Drug Testing and Analysis, 2026.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.