SLU-PP-332

SLU-PP-332 is a lab-made small molecule that switches on all three estrogen-related receptors (ERRα, ERRβ and ERRγ), which run the cell’s energy and mitochondria programs. Known in research as an exercise mimetic, it sets off the gene signal muscle gets from aerobic exercise, with its strongest pull on ERRα.

SLU-PP-332 is studied in muscle, fat and heart research. In the founding study, sedentary mice given it for a week ran about 70% longer and 45% further than controls (Billon et al., 2023, ACS Chemical Biology).

Research Applications

• Studied in endurance and exercise-mimetic models
• Relevant in research on fat oxidation and energy expenditure
• Examined in mitochondrial function and muscle-fibre studies
• Applied in ERR signalling and cardiac-metabolism work

Each vial holds 10 mg at ≥99% HPLC purity.

Supplied as a lyophilized powder for stability.

See also: AICAR 50 mg, MOTS-c, and 5-Amino-1MQ.

Scientific Background

The estrogen-related receptors ERRα, ERRβ and ERRγ are orphan nuclear receptors. Despite their name they do not respond to estradiol; they act as constitutively active transcription factors that, together with the PGC-1 co-activators, control mitochondrial biogenesis, fatty acid and glucose metabolism, and oxidative phosphorylation in muscle, heart, kidney and fat.

Because ERRα has a largely collapsed ligand-binding pocket, it was long regarded as an intractable target for synthetic agonists. The first ERR agonists, the phenolic acyl hydrazones GSK4716 and GSK9089, were selective for ERRβ and ERRγ.

SLU-PP-332 came from structure-based optimisation of the GSK4716 scaffold, swapping its isopropylphenyl group for a naphthalene ring. The result is a pan-ERR agonist with its highest potency at ERRα and enough in vivo exposure to serve as a chemical tool in laboratory models.

SLU-PP-332 Structure

Compound Class: Synthetic small-molecule pan-ERR agonist (phenolic acyl hydrazone)
Chemical Name: 4-Hydroxy-N’-[(E)-naphthalen-2-ylmethylidene]benzohydrazide
Molecular Formula: C₁₈H₁₄N₂O₂
Molecular Weight: 290.32 g/mol
CAS Number: 303760-60-3
PubChem CID: 5338394

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