SLU-PP-332

SLU-PP-332 is a synthetic pan-agonist for all three estrogen-related receptors (ERRα, ERRβ, ERRγ) — nuclear receptors that act as master regulators of mitochondrial biogenesis and oxidative metabolism. Unlike classical estrogen receptors, ERRs are activated by metabolic signals, not estrogen. SLU-PP-332 activation drives transcription of genes involved in fatty acid oxidation, mitochondrial biogenesis via the PGC-1α pathway, and oxidative phosphorylation — pharmacologically inducing a "trained endurance" metabolic phenotype.

Skaggs Institute 2023: Mice treated with SLU-PP-332 showed 70% increase in running distance and elevated resting metabolic rate.

Mitochondrial biogenesis: Upregulation of PGC-1α, SIRT1, and downstream oxidative phosphorylation gene networks.

Cardiac protection: Improved cardiac hypertrophy and heart failure models via ERR-mediated fatty acid utilization.

Exercise mimetic: Behavioral and molecular overlap with endurance exercise training observed in multiple tissue types.

Selectivity: Pan-ERR activation may offer broader metabolic modulation than selective ERRα agonists studied previously.