SLU-PP-322

SLU-PP-332 is a potent synthetic pan-agonist of the estrogen-related receptor (ERR) family and serves as a valuable research tool for investigating metabolic regulation and energy homeostasis. The compound was developed through structure–activity relationship (SAR) studies to activate the orphan nuclear receptors ERRα, ERRβ, and ERRγ, with the greatest potency toward ERRα.

The ERR family comprises three constitutively active transcription factors that regulate genes involved in oxidative metabolism, mitochondrial function, fatty acid metabolism, and energy expenditure. Although they share structural similarity with estrogen receptors and regulate some overlapping target genes, ERRs do not bind estrogen.

In preclinical mouse models, SLU-PP-332 has been shown to:

• Increase energy expenditure
• Enhance fatty acid oxidation
• Reduce adiposity
• Improve insulin sensitivity without altering food intake

These findings resemble several metabolic adaptations associated with endurance exercise.

SLU-PP-332 also increases mitochondrial function and cellular respiration in cultured skeletal muscle cells, consistent with the established role of ERR signalling in regulating mitochondrial metabolism.